Clinical Neurochemistry – Flashcards
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What is a receptor?
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Protein molecule; Located in plasma membrane; Produces a change when ligand binds to it
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Distinguish between receptors and acceptors.
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Receptor: both binding and signal generation; Accepter: no biological impulse is generated
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Ligand examples include:
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Peptides, neurotransmitter, hormones, drugs, toxins
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How have receptors been studied?
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Historically: dissect animals, add agonist/antagonist and watch reaction; Newer: measure ligand binding to homogenate; Intracellular stimulation and recording via microelectrodes
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Name two major types of receptors.
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1. Ligand-gated/ionotropic; 2. G protein-coupled; Metabotropic
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Describe ligand-gated/ionotropic channels.
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Multiple sub-units with central pore; Passage of ions (Na, K, Ca, Cl); Fast effect (milliseconds)
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Describe Metabotropic channels.
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Coupled with G-proteins; slower responses (seconds to minutes); *Modulatory/dampening/enhancing.*
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(Ionotropic/Metabotropic) channels are faster.
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Ionotropic
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List some examples of ionotropic receptors
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Nicotinic; NMDA; GABA-A; 5-HT3
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List some examples of metabotropic receptors.
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Muscarinic cholinergic; Adrenegric; Dopaminergic; Serotonergic; Opiate Gs, Gi, Gq, G12
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2nd messenger proteins are associated with (ionotropic/metabotropic) channels.
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Metabotropic channels
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Describe differences between neurotransmitters and hormones
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Small, easy to make, easy to use, easy to recycle
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Describe a neurotransmitter
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Stored in presynaptic neuron; Released via depolarization of the presynaptic neuron (Ca mediated); Able to bind with a specific receptor nearby on a postsynaptic neuron
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List major neurotransmitter types
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Amino acids; monoamines (Catacholamines; Indolamines; Others)
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List common amino acid neurotransmitters
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*Glutamate*; aspartate; D-serine; *GABA; Glycine*
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List common catecholamine neurotransmitters.
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*Dopamine, norepinephrine, epinephrine*
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List common indolamine neurotransmitters
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*Serotonin, melatonin*
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List other monoamines not listed in other categories.
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*Acetylcholine*; Histamine
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GABA is (inhibitory/excitatory) whereas glutamate is (inhibitory/excitatory).
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GABA=inhibitory; Glutamate=excitatory
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Alcohol acts on __ receptors, so without alcohol an alcoholic is constantly in an (inhibitory/excitatory) state.
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GABA receptors; W/o alcohol, in an excitatory state because GABA is inhibitory
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Describe the importance of glutamate.
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Amino acid neurotransmitter; Excitatory role in many things (e.g. *memory*)
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What is the most common neurotransmitter? *KNOW*
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Glutamate (EXCITATORY!)
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What are the four types of Glutamate receptors and what types of channels are they?
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*Ionotropic: NMDA, AMPA, Kainate*; Metabotropic: mGluR
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___ allow quick entry of Ca and __ allow quick entry of Na into a cell.
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NMDA allows Ca; AMPA and Kainate allow Na [Glutamate receptors]
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List some glutamatergic drugs.
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Ketamine; Memantine; Amantadine; Riluzole
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Ketamine
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Aka Special K; NMDA antagonist; used recreationally; very powerful
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Memantine
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Used in dementia; NMDA receptor antagonist; Alzheimers: glutamate-associated excitotoxicity theory so this drug acts against that;
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Riluzole
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NMDA antagonist; slows down progression of ALS
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Amantadine
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Antiviral; Also used in Parkinson's
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List some excitatory amino acids.
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Glutamate, aspartate (DEPOLARIZE)
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List some inhibitory amino acids.
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GABA, Glycine (hyperpolarize)
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GABA and Glycine
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Inhibitory; Used by at least 1/4th of neurons; Roles in sleep, pain and anxiolysis
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___ is involved in most inhibitory receptors.
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Chloride (opened by GABA)
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GABA is made from __, and the rate is limited by ___.
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Made from glutamate; Rate limited by glutamic acid decarboxylase
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GABA-A is (ionotropic/metabotropic) whereas GABA-B is (ionotropic/metabotropic)
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GABA-A=ionotropic; GABA-B=metabotropic
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Benzos act on (frequency/duration) whereas barbiturates act on (frequency/duration). *KNOW*
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Benzos=frequency; Barbiturates=duration
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Smaller tranquilizers include:
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Benzos and barbiturates--both potentiate GABA effect (cause more inhibition)
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(Barbiturates/benzos) are more potent.
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Barbiturates--more lethal!
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T/F: If there's no GABA in the system, can still get an inhibitory effect from benzos.
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FALSE. Benzos just amplify GABA; Whereas Barbiturates act irrespective of GABA (act like GABA on their own)
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Zolpidem and Zaleplon
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Aka Ambien/Lunesta; Attach to the same site (Benzo site) but non-benzo molecules. Similar to Benzos. Ambien used for sleep (complication: can sleepwalk)
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GABA-B drugs include:
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Baclofen (muscle relaxant); GHB (roofies; aka liquid G, fanasy...)
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T/F: Monoamines are much less common than amino acids.
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TRUE
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After glutamate, the most common neurotransmitter is:
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GABA
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Catecholamines
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Derived from tyrosine; Include dopamine, epinephrine (adrenaline) and norepinephrine (noradrenaline)
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The rate limiting step of creating catecholamines is: *KNOW*
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Tyrosine Hydroxylase (uses Tyrosine and makes DOPA which makes Dopamine which makes NE)
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(D1/D2) dopamine receptors are used for reward and cognition, whereas (D1/D2) is used for antipsychotic effects.
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D1=reward/cognition; D2=antipsychotic effects
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Clinical implications of decreased dopamine include:
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Parkinson's (Decreased dopamine from substantia nigra); ADHD (dopamine deficiency); Drug addiction (Reward from dopamine); Psychosis (from dopamine excess)
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__ is the enzyme that converts DOPA to Dopamine.
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DOPA decarboxylase
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Norepinephrine manifest in
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Altertness, arousal, and influences on reward system; Found in Locus Coeruleus with multiple projections
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Adrenergic receptors include:
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Alpha 1: Vasoconstriction; Alpha 2: Autoregulation
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Epinephrine is more (peripheral/central) and released from ___
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Peripheral; Released by adrenal medulla
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Epinephrine
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Used in fight or flight; Not psychoactive
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Describe the first step of creating serotonin.
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First: tryptophan becomes 5-Hydroxytryptophan via Tryptophan hydroxyls (RATE-LIMITING); THEN 5-hydroxytryptophan becomes serotonin via aromatic acid decarboxylase
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__ is the rate limiting step of creating serotonin
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Tryptophan hydroxylation
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Tryptophan can be found in: (list foods)
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Red meat, dark chocolate; red wine; milk, eggs
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Disorders related to serotonin include:
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Depression, anxiety, OCD, Schizophrenia, eating disorders, migraines
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Drugs that affect serotonin include:
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Antidepressants; Hallucinogenic drugs (LSD, psilocybin); Anxiolytics (buspirone); Atypical antipsychotics; Antiemetics (-setrons); Antimigrains (-triptans)
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Melatonin
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Acts on seratonin
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Acetylcholine mostly resides in the __. *KNOW*
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Nucleus Basalis, which projects to the neocortex and other areas
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Histamine
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Mostly involved in periphery (allergies); Tuberomamillary nucleus of posterior hypothalamus to various parts of the brain; Activation=alertness; Antagonism=sedation
