Receptors and Neurotransmitters of the CNS

Neurotransmission

Synapses and neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission

1. Neurotransmitters are synthesized and packaged into vesicles Vesicles Female Genitourinary Examination at the body of the neuron or at the synaptic terminal.
2. Neurotransmitter vesicles Vesicles Female Genitourinary Examination in the body of the neuron are transported to the synaptic terminal via axons Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Nervous System: Histology.
3. An action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential is conducted through the axon and it reaches the synaptic terminal.
4. The action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential induces the opening of voltage-gated calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ( Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)⁺²) channels Channels The Cell: Cell Membrane.
5. Influx of Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)⁺² induces the migration of vesicles Vesicles Female Genitourinary Examination to the synaptic membrane.
6. Vesicles Vesicles Female Genitourinary Examination fuse with the synaptic membrane and release their neurotransmitters into the synaptic cleft Synaptic cleft Synapses and Neurotransmission.
7. Neurotransmitters interact with their receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on the membrane of the postsynaptic cell.

Overview of Neurotransmitters

More than 500 unique neurotransmitters have been identified in humans.

Characteristics

• Proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis stored in synaptic vesicles Vesicles Female Genitourinary Examination
• Chemical messengers that transmit signals from a neuron to a target cell
• Dimensions of neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission:
  • Space: local versus distant targets
  • Time: slow versus fast onset
  • Function: inhibition versus activation

Effects

• Full agonist: The neurotransmitter strongly binds to the receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors having the greatest effect on gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription.
• Partial agonist: weaker binding to the receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. May work as a weak agonist or compete with the agonist to decrease the potential of the agonist
• Antagonist: no intrinsic effect. When an antagonist is bound, the receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors is rendered inactive.
• Inverse agonist: has the opposite effect to that exerted by agonists and may suppress spontaneous receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors signaling

Classes

• Amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids:
  • GABA
  • Glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids
  • Glycine Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Synthesis of Nonessential Amino Acids
• Cholinergic: acetylcholine (ACh)
• Monoamines (derived from aromatic amino acids Aromatic amino acids Amino acids containing an aromatic side chain. Basics of Amino Acids):
  • Serotonin
  • Histamine
• Catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones:
  • Dopamine
  • Norepinephrine (NE)
  • Epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs
• Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics:
  • Dynorphins
  • Endorphins
  • Enkephalins
• Soluble gasses:
  • NO
  • CO

High-yield CNS Neurotransmitters

5-Hydroxytryptamine (5-HT)/serotonin

• The majority of serotonin-producing neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology are located in the raphe Raphe Testicles: Anatomy nuclei in the brainstem.
• Upon propagation Propagation Propagation refers to how the electrical signal spreads to every myocyte in the heart. Cardiac Physiology of an action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential down the neuron → storage vesicles Vesicles Female Genitourinary Examination fuse with the presynaptic membrane Presynaptic membrane Synapses and Neurotransmission → release of neurotransmitters into the synaptic cleft Synaptic cleft Synapses and Neurotransmission
• 5-HT activity is terminated by serotonin transporter → reuptake of 5-HT into the serotonergic nerve terminals
• 5-HT can then be reloaded into vesicles Vesicles Female Genitourinary Examination by vesicular monoamine transporter (VMAT) 2 or metabolized by monoamine oxidase Oxidase Neisseria (MAO), which has 2 isoforms:
  • MAO-A metabolizes tyramine, NE, dopamine, and 5-HT.
  • MAO-B preferentially metabolizes dopamine.

Catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones

• Catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones are synthesized in the nerve terminal.
• Upon propagation Propagation Propagation refers to how the electrical signal spreads to every myocyte in the heart. Cardiac Physiology of an action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential down the neuron → storage vesicles Vesicles Female Genitourinary Examination fuse with the presynaptic membrane Presynaptic membrane Synapses and Neurotransmission → release of neurotransmitters into the synaptic cleft Synaptic cleft Synapses and Neurotransmission
• Dopamine action can be terminated by the dopamine transporter (DAT) → reuptake of dopamine into dopaminergic nerve terminal
• NE action can be terminated by the NE transporter (NET) → reuptake of NE into the noradrenergic nerve terminal
• Dopamine or NE can then be reloaded into vesicles Vesicles Female Genitourinary Examination by VMAT2 or degraded by MAO or catechol-O-methyltransferase (COMT), which are located outside the noradrenergic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology.
• Dopamine:
  • Regulates attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment, impulse control, locomotor activity, memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment, cognition, reward-seeking behavior, and is involved with addiction Addiction Substance use disorders are a significant cause of morbidity and mortality, especially among adolescents and young adults. A substance-related and addictive disorder is the continued use of a substance despite harmful consequences; these include significant impairment to one’s health or relationships or failure to fulfill major responsibilities at work, school, or home because of substance use. Substance-Related and Addictive Disorders
  • 4 dopaminergic neuron pathways exist.
• NE:
  • Derived from dopamine
  • Noradrenergic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology originate in the locus Locus Specific regions that are mapped within a genome. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of chromosome 6. Many well known genetic loci are also known by common names that are associated with a genetic function or hereditary disease. Basic Terms of Genetics coeruleus of the pons Pons The front part of the hindbrain (rhombencephalon) that lies between the medulla and the midbrain (mesencephalon) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the cerebellum to the cerebrum. Brain Stem: Anatomy.
  • Noradrenergic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology project to the cerebellum Cerebellum The cerebellum, Latin for “little brain,” is located in the posterior cranial fossa, dorsal to the pons and midbrain, and its principal role is in the coordination of movements. The cerebellum consists of 3 lobes on either side of its 2 hemispheres and is connected in the middle by the vermis. Cerebellum: Anatomy, cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex: Anatomy, hippocampus, hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus, and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy.
  • Involved in anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, arousal, attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment, cognition, mood, and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways

Glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids

• Major excitatory amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids
• Synthesized via 2 pathways in the glutaminergic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology:
  • Conversion of glutamine Glutamine A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. Synthesis of Nonessential Amino Acids by mitochondrial glutaminase
  • Conversion of α-ketoglutarate by mitochondrial GABA transaminase Transaminase A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Catabolism of Amino Acids (GABA-T)
• Glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids is loaded into storage vesicles Vesicles Female Genitourinary Examination by the vesicular glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids transporter (VGlut).
• Glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids is also recycled by neighboring astrocytes Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system – the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from ‘star’ cells) are irregularly shaped with many long processes, including those with ‘end feet’ which form the glial (limiting) membrane and directly and indirectly contribute to the blood-brain barrier. They regulate the extracellular ionic and chemical environment, and ‘reactive astrocytes’ (along with microglia) respond to injury. Nervous System: Histology.
• Neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission → storage vesicles Vesicles Female Genitourinary Examination fuse with the presynaptic membrane Presynaptic membrane Synapses and Neurotransmission → release of neurotransmitters into the synaptic cleft Synaptic cleft Synapses and Neurotransmission
• Glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids activity is terminated by excitatory amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids transporter (EAAT) → reuptake of glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids into glutamatergic nerve terminal
• Involved in cognition, learning, memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment, neuronal cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death, and synaptic plasticity

Gamma-aminobutyric acid and GABAergic interneurons

• GABA is the main inhibitory neurotransmitter in the CNS.
• GABAergic interneurons: local circuit inhibitory neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology that regulate glutamatergic neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission → binding of GABA to GABA_B receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on glutamatergic terminals inhibits glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids release
• GABA hyperpolarizes or inhibits the cell by opening the chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes ion (Cl^–) channels Channels The Cell: Cell Membrane.

Receptors

Definition

• Complexes of protein subunits embedded into the postsynaptic cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane
• Receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors are charged with sensing relevant stimuli from the environment and converting that signal into other forms of intracellular signaling to produce a response.

5-Hydroxytryptamine (serotonin) receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors

• Subtypes: 5-HT₁, 5-HT₂, 5-HT₃, 5-HT₄, 5-HT₅, 5-HT₆, 5-HT₇
• The various 5-HT receptors 5-HT receptors First-Generation Antipsychotics are understood to have a role in the presentation of depression as well as in the response to antidepressants.

Dopaminergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors

• Subtypes: D₁, D₂, D₃, D₄, and D₅
• D₁, D₂, and D₃ are pharmacologic targets.
• D₁-like receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (subtypes 1 and 5) are excitatory.
• D₂-like receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (subtypes 2, 3, and 4) are inhibitory.
• D₂ receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors are expressed on dopaminergic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology as presynaptic autoreceptors and postsynaptic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors.

Adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (adrenoceptors or noradrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors)

• All adrenoceptors are G-protein coupled receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors.
• Targets of catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones as well as adrenergic and antiadrenergic Antiadrenergic Antiadrenergic agents are drugs that block the activity of catecholamines, primarily norepinephrine (NE). There are 2 major types of adrenergic receptors-alpha and beta receptors, and there are several subtypes of each. Antiadrenergic Drugs medications
• 2 families of adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
  • α-Adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (α₁ and α₂ subtypes)
  • β-Adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (β1, β2, and β3 subtypes)
• α₁-Receptors are postsynaptic and excitatory in nature:
  • α₁-Receptor stimulation:
    • Activates the enzyme phospholipase C Phospholipase C A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of glycerophospholipids. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of phosphatidylcholine, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of phosphatidylinositols. Pseudomonas →
    • Generates inositol triphosphate (IP₃) and diacylglycerol Diacylglycerol Second Messengers ( DAG DAG Second Messengers) as secondary messengers → 
    • Causes ↑ Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ levels intracellularly → 
    • Smooth muscle contraction Smooth muscle contraction Smooth muscle is primarily found in the walls of hollow structures and some visceral organs, including the walls of the vasculature, GI, respiratory, and genitourinary tracts. Smooth muscle contracts more slowly and is regulated differently than skeletal muscle. Smooth muscle can be stimulated by nerve impulses, hormones, metabolic factors (like pH, CO2 or O2 levels), its own intrinsic pacemaker ability, or even mechanical stretch. Smooth Muscle Contraction
• α₂-Receptors are presynaptic and inhibitory in nature ( trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation catecholamine reuptake):
  • α₂-Receptor stimulation:
    • Inhibits the enzyme adenylyl cyclase →
    • ↓ Levels of the secondary messenger cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors →
    • Ultimately blocks the presynaptic release of NE →
    • ↓ Adrenergic stimulation
• All 3 β-receptor subtypes are excitatory in nature:
  • β-Receptor stimulation: stimulates adenylyl cyclase → ↑ cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors → triggers target cell effects

Glutamatergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors

• Ionotropic glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
  • α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA): activated by glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids → Na⁺ influx → rapid depolarization Depolarization Membrane Potential (excitatory postsynaptic potential (EPSP)) → EPSP expels Mg²⁺ from the N-methyl-D-aspartate (NMDA) receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ion channel
    • Depolarization Depolarization Membrane Potential of glutamatergic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology → increased brain-derived neurotrophic factor (BDNF) synthesis Synthesis Polymerase Chain Reaction (PCR)
  • Kainate: activated by glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids → Na⁺ influx → fast EPSP
  • NMDA: AMPA-induced EPSP → Mg²⁺ is expelled from the NMDA receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (NMDAr) + glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids and glycine Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Synthesis of Nonessential Amino Acids (cofactor) bind BIND Hyperbilirubinemia of the Newborn to NMDArs → NMDArs open →  Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ influx → slower prolonged depolarization Depolarization Membrane Potential
    • NMDA heteroreceptors located on the GABAergic interneurons stimulate GABA release.
    • Overexcitation of NMDArs on glutamatergic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology → ↓ BDNF synthesis Synthesis Polymerase Chain Reaction (PCR)
    • Note that excessive Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ influx causes neuronal toxicity Toxicity Dosage Calculation and apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage.
• Metabotropic glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (mGlurs) (clinical significance unknown):
  • Group I: mGlur1, 5
  • Group II: mGlur2, 3
  • Group III: mGlur4, 6–8

Gamma-aminobutyric acidergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors

• Macromolecular complexes made up of 5 protein subunits
• Allow entry of Cl^– into the cell → inhibition of neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission
• IV anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts target different points in the channel, increasing either the duration or frequency of Cl^– flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure through the open channel.
• GABA_A:
  • Ionotropic transmembrane Cl^– channel that opens via receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors activation
  • Causes hyperpolarization Hyperpolarization Membrane Potential of the neuron to suppress excitability Excitability Skeletal Muscle Contraction
  • Binding to α₁ results in sedation, whereas binding to α₂ results in diminished anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder.
• GABA_B:
  • G-protein coupled receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors that inhibits adenylyl cyclase, opens K⁺ channels Channels The Cell: Cell Membrane, and closes Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ channels Channels The Cell: Cell Membrane
  • Functions as an autoreceptor
  • Impaired GABA_B functioning is linked with various neuropsychiatric disorders such as anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, depression, addiction Addiction Substance use disorders are a significant cause of morbidity and mortality, especially among adolescents and young adults. A substance-related and addictive disorder is the continued use of a substance despite harmful consequences; these include significant impairment to one’s health or relationships or failure to fulfill major responsibilities at work, school, or home because of substance use. Substance-Related and Addictive Disorders, and cognitive impairment.

Clinical Relevance

• Parkinson disease Parkinson disease Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder. Although the cause is unknown, several genetic and environmental risk factors are currently being studied. Individuals present clinically with resting tremor, bradykinesia, rigidity, and postural instability. Parkinson’s Disease: a degenerative disease of the basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy characterized by a clinical syndrome manifesting with bradykinesia Bradykinesia Parkinson’s Disease (slowed movements), cogwheel rigidity Cogwheel Rigidity Parkinson’s Disease, and “pill-rolling” tremors at rest. The pathophysiology of Parkinson disease Parkinson disease Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder. Although the cause is unknown, several genetic and environmental risk factors are currently being studied. Individuals present clinically with resting tremor, bradykinesia, rigidity, and postural instability. Parkinson’s Disease includes degeneration of the dopaminergic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology of the substantia nigra Substantia nigra The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce dopamine, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored melanin is a by-product of dopamine synthesis. Basal Ganglia: Anatomy and subsequent loss of central dopamine supply. Treatment is with drugs such as levodopa Levodopa The naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. Parkinson’s Disease Drugs/carbidopa, MAO-B inhibitors, and dopamine agonists, which restore dopaminergic activity. As of today, there are no curative treatments, and the management focuses on symptom amelioration.
• Antidepressants: medications originally used to treat depression. Based on the theory of neurotransmitter imbalance, antidepressants seek to influence mood by changing the levels of specific neurotransmitters in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification. Medications can be grouped into classes such as selective serotonin reuptake inhibitors Selective Serotonin Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants ( SSRIs SSRIs Serotonin Reuptake Inhibitors and Similar Antidepressants), serotonin-NE reuptake inhibitors ( SNRIs SNRIs Serotonin Reuptake Inhibitors and Similar Antidepressants), and several others based on their effects. Antidepressants are indicated as 1st-line treatment for the management of anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder disorders and major depressive disorder Major depressive disorder Major depressive disorder (MDD), commonly called depression, is a unipolar mood disorder characterized by persistent low mood and loss of interest in association with somatic symptoms for a duration of ≥ 2 weeks. Major depressive disorder has the highest lifetime prevalence among all psychiatric disorders. Major Depressive Disorder (MDD). Therapeutic response to antidepressants takes 2–4 weeks and the full benefit is not seen until up to 8 weeks. Overdose can be life threatening; thus, the signs and symptoms of SSRI/SNRI overdose should be recognized promptly.
• Antipsychotics (neuroleptics): drugs used to treat psychotic disorders and alleviate agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus, mania Mania A state of elevated excitement with over-activity sometimes accompanied with psychotic symptoms (e.g., psychomotor agitation, inflated self esteem and flight of ideas). It is often associated with mental disorders (e.g., cyclothymic disorder; and bipolar diseases). Bipolar Disorder, and aggression Aggression Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism. Oppositional Defiant Disorder. Antipsychotics are divided into 1st-generation antipsychotics and atypical or 2nd-generation antipsychotics. Both classes of drugs act on dopamine receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. Notable side effects of antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics agents include movement disorders, dose-related sedation, and metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome.
• Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines: medications that act on the GABA_A receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors to produce inhibitory effects on the CNS. Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines potentiate GABA activity. Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines have anxiolytic, muscle-relaxant, hypnotic, sedative, and anticonvulsant Anticonvulsant Anticonvulsant drugs are pharmacological agents used to achieve seizure control and/or prevent seizure episodes. Anticonvulsants encompass various drugs with different mechanisms of action including ion-channel (Na+ and Ca+2) blocking and GABA reuptake inhibition. First-Generation Anticonvulsant Drugs properties and are generally not recommended for long-term use, as individuals may develop physiological and psychological dependence. Side effects may include cognitive impairment, somnolence, and respiratory depression.