PCOL Exam 2: Neurotransmission & Basic Neurochemistry

Gamma amino-butyric acid
Major inhibitory transmitter in brain

Enzyme=glutamic acid decarboxylase
COOH removed from glutamic acid to make GABA

Reuptake=major means of inactivation
Broken down by GABA-transaminase
Catabolism blocked by gamma vinyl GABA

2 receptor subtypes
A=ligand-gated ion channel
B=GPCR

increase in membrane permeability to Cl-
Hyperpolarize membrane

Major inhibitory NT in spinal cord
Increases Cl- conductance to hyperpolarize the membrane

GABA and glycine

Glutamic acid and Aspartic acid

Major excitatory NT in brain
Synthesized in neurons from precursor glutamine

Ligand-gated ion channels (influx of Na depolarizes membrane)
1) NMDA
2) AMPA
3) kainate
Metabotropic
1) mGLuR 1-8

High affinity reuptake transmitters

MSG=monosodium glutamate
Kainic acid=neurotoxin

Enzyme=choline acetyltransferase
Acetyl CoA + Choline makes ACh + CoA
Rate-limiting step=choline uptake

Enzymatic breakdown only
Hydrolysis to yield acetate and choline
True=acetylcholinesterase
Pseudo=butyrylcholinesterase
Choline may be reuptaken and reused
Cholinesterase inhibitors block ACh breakdown

2 families
1) Nicotinic=ligand-gated ion channels
2) Muscarinic=GPCRs, M1-M5

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

Dopamine
Norepinephrine
Epinephrine

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)

Cofactor=tetrahydrobiopterin
Rate-limiting enzyme
Unique to catecholamine containing neurons

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

Amphetamine and tyramine
Can indirectly elicit Ca dependent exocytosis of catecholamines

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

Locus ceruleus=1500 neurons located in pons area
5 major noradrenergic tracts that project to many brain areas

1) Ultra short neurons
2) Intermediate length neurons
3) Long-length projections

Found in retina and olfactory bulb
Axons don’t leave structures they originate in

hypothalamus to pituitary
Pituitary=mediates endocrine functions

1) Substantia nigra pars compacta A9 neurons
2) Ventral tegumental area A10 neurons

Project from substantia nigra to striatum
Mediate extrapyramidal motor functions
Die in Parkinson’s disease
May be overly active in Huntington’s disease

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

D1 like=stimulate adenylate cyclase (D1, D5)
D2 like=don’t stimulate AC (D2, D3, D4)
All GPCRs

Alpha receptors (1abd, 2abc)
Beta receptors (1, 2, 3)
All GPCRs

1) Tryptophan + OH->5-hydroxytryptophan
E=tryptophan hydroxylase
2) 5-hydroxytryptophan – COOH->5-hydroxytryptamine (serotonin)
E=L-aromatic amino acid decarboxylase

1) Reuptake=fast, major means (blocked by SSRIs and some tricyclic antidepressants)
2) Metabolism by MAO, then to 5-HIAA

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)

Nuceli of midline raphe (extends axons to most of brain)
Autoreceptors inhibit neuronal firing and transmitter release

Histidine – COOH=histamine
E=histidine decarboxylase

By histamine N-methyltransferase enzyme

In hypothalamus
Arousal, attention, feeding behavior, memory

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)

Important in spinal cord pain transmission
Also regional localization in sensory and motor areas of brain