PCOL Exam 2: Neurotransmission & Basic Neurochemistry

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GABA meaning
Gamma amino-butyric acid
Major inhibitory transmitter in brain
GABA synthesis
Enzyme=glutamic acid decarboxylase
COOH removed from glutamic acid to make GABA
GABA inactivation
Reuptake=major means of inactivation
Broken down by GABA-transaminase
Catabolism blocked by gamma vinyl GABA
GABA receptor subtypes
2 receptor subtypes
A=ligand-gated ion channel
GABA-A mechanism
increase in membrane permeability to Cl-
Hyperpolarize membrane
Major inhibitory NT in spinal cord
Increases Cl- conductance to hyperpolarize the membrane
Inhibitory NTs
GABA and glycine
Excitatory NTs
Glutamic acid and Aspartic acid
Glutamic acid basics
Major excitatory NT in brain
Synthesized in neurons from precursor glutamine
Glutamic acid receptor subtypes
Ligand-gated ion channels (influx of Na depolarizes membrane)
3) kainate
1) mGLuR 1-8
Glutamic acid inactivation
High affinity reuptake transmitters
Receptor agonists for glutamic acid
MSG=monosodium glutamate
Kainic acid=neurotoxin
ACh synthesis
Enzyme=choline acetyltransferase
Acetyl CoA + Choline makes ACh + CoA
Rate-limiting step=choline uptake
ACh inactivation
Enzymatic breakdown only
Hydrolysis to yield acetate and choline
Choline may be reuptaken and reused
Cholinesterase inhibitors block ACh breakdown
ACh receptor subtypes
2 families
1) Nicotinic=ligand-gated ion channels
2) Muscarinic=GPCRs, M1-M5
ACh in CNS disease states
Alzheimers=death of ACh neurons originating in nucleus basalis of Meyner and projecting to cerebral cortex
May use cholinesterase inhibitors to prevent Ach inactivation and potentiate NTs effect
Catecholamine NTs
1) Tyrosine + OH ->L-Dopa
E=tyrosine hydroxylase
2) L-Dopa – COOH->Dopamine
E=L-aromatic amino acid decarboxylase
3) Dopamine + OH ->Norepinephrine
E=Dopamine beta hydroxylase (DBH)
4) Norepi + CH3 ->Epinephrine
E=Phenylethanolamine-N-methyltransferase (PNMT)
Tyrosine hydroxylase
Rate-limiting enzyme
Unique to catecholamine containing neurons
L-aromatic amino acid decarboxylase
Found everywhere in body
Decarboxylates many L-aromatic AAs
Also known as DOPA decarboxylase
in membrane of noradrenergic storage granules
little found in brain since little epinephrine is in CNS
Found mostly in periphery in adrenal medulla
Sympathomimetic drugs
Amphetamine and tyramine
Can indirectly elicit Ca dependent exocytosis of catecholamines
Catecholamine Inactivation
1) Rapid reuptake into presynaptic terminal
(blocked by cocaine & tricyclic antidepressants)
2) Slower enzymatic degradation by:
a) MAO=monoamine oxidase
b) COMT=catechol-O-methyl transferase
Primarily interneuronal, in cytoplasm of nerve terminal
Metabolizes catecholamine to corresponding aldehyde which converts to acid
extraneuronal metabolism
places a methyl group on m-hydroxyl position of catecholamine
Norepi neuron pathway
Locus ceruleus=1500 neurons located in pons area
5 major noradrenergic tracts that project to many brain areas
Dopamine neuron major classes
1) Ultra short neurons
2) Intermediate length neurons
3) Long-length projections
ultra short neurons
Found in retina and olfactory bulb
Axons don’t leave structures they originate in
intermediate length neurons
hypothalamus to pituitary
Pituitary=mediates endocrine functions
long-length projections
1) Substantia nigra pars compacta A9 neurons
2) Ventral tegumental area A10 neurons
A9 neurons
Project from substantia nigra to striatum
Mediate extrapyramidal motor functions
Die in Parkinson’s disease
May be overly active in Huntington’s disease
A10 neurons
Project from VTA to limbic areas of brain
Mediate pleasure/reward
Excessive activity implicated in schizophrenia
Present on pre-synaptic neuron for NT released
Inhibitory feedback regulation of that neuron’s firing rate and NT release
Dopamine receptors
D1 like=stimulate adenylate cyclase (D1, D5)
D2 like=don’t stimulate AC (D2, D3, D4)
Norepi receptors
Alpha receptors (1abd, 2abc)
Beta receptors (1, 2, 3)
Serotonin synthesis
1) Tryptophan + OH->5-hydroxytryptophan
E=tryptophan hydroxylase
2) 5-hydroxytryptophan – COOH->5-hydroxytryptamine (serotonin)
E=L-aromatic amino acid decarboxylase
Serotonin inactivation
1) Reuptake=fast, major means (blocked by SSRIs and some tricyclic antidepressants)
2) Metabolism by MAO, then to 5-HIAA
Serotonin receptor subtypes
14 total receptors
1) 5-HT (1A-1F)
2) 5-HT (2A-2C)
3) 5-HT (3)
4) 5-HT (4)
5) 5-HT (5A, 5B)
6) 5-HT (6)
7) 5-HT (7)
All GPCRs except 5-HT (3)
serotonin pathways in CNS
Nuceli of midline raphe (extends axons to most of brain)
Autoreceptors inhibit neuronal firing and transmitter release
Histamine synthesis
Histidine – COOH=histamine
E=histidine decarboxylase
Histamine metabolism
By histamine N-methyltransferase enzyme
Histamine neurons in CNS
In hypothalamus
Arousal, attention, feeding behavior, memory
Enkephalins and endorphins
Opiate-like peptides
Exist in specific CNS neuronal pathways with varying regional distribution
Act as receptors for opiate drugs
Blocked by opiate antagonist drugs (naloxone)
Substance P
Important in spinal cord pain transmission
Also regional localization in sensory and motor areas of brain
Categories: Neurochemistry