Neurotransmitters & Receptors

Acetyl-CoA

Enzyme that supplies acetate for synthesis of acetyl choline, begins the Kreb Cycle

Choline acetyltransferase (ChAT)

Enzyme that transfers acetate ion from acetyl-CoA to choline

Acetylcholinesterase (AChE)

Enzyme that breaks apart acetylcholine molecule

Acetylcholine controls which functions in the brain?

REM sleep, memory, facilitating learning & electrical rhythms of the hippocampus

Botulinum toxin

Acetylcholine antagonist, prevents release of neurotransmitters by the terminal buttons

Black widow spider venom

Venom triggers release of acetylcholine in copious amounts, toxic

Hemicholinium

Drug that inhibits uptake of choline

Myasthenia gravis

Autoimmune disease that prevents muscular and neuronal communication

Neostigmine

Used to treat Myasthenia gravis by inhibiting activity of acetylcholinesterase

Nicotine receptor

Ionotropic acetylcholine receptor

- Blocked by curare

Muscarinic receptor

Metabotropic acetylcholine receptor

- Blocked by atropine

Atropine

Drug that inhibits muscarinic acetylcholine receptors

Curare

Drug that blocks nicotinic acetylcholine receptors

Monamines...

Catecholamines & Indolamines

Catecholamines...

Dopamine, Norepinephrine, & Epinephrine

Indolamines

Serotonin

Tyrosine

Starting molecule for production of catecholamines

Tyrosine hydroxylase

Enzyme that converts Tyrosine to L-DOPA

- Rate limiting

- Adds OH group

DOPA decarboxylase

Enzyme that converts L-DOPA into Dopamine

- Removes a COOH group

- AKA 5HTP decarboxylase

Dopamine β-hydroxylase

Enzyme that converts Dopamine to Norepinephrine

- Not present in dopaminergic neurons

Phenylethanolamine N-methyltransferase

Enzyme that converts Norepinephrine to Epinephrine

AMPT

Drug that blocks activity of tyrosine hydroxylase. Can't make catecholamines at all

Fusaric acid

Drug that inhibits the activity of Dopamine β-hydroxylase, can't make norepinephrine

Monoamine oxidase (MAO)

Inactivates catecholamines free within nerve terminals (intracellular)

Catechol-O-methyltransferase (COMT)

Degrades catecholamines in the extracellular space (cleft)

MAO-A

Selective for inhibiting NE and serotonin

MAO-B

Inhibits Dopamine & broad spectrum of phenylethylamines

Moclobemide

Drug that inhibits activity of MAO-A; increase noradrenergic tone

Deprenyl

Drug that blocks activity of MAO-B; increase dopaminergic tone

Mesocortical system

Major dopamine pathway responsible for Cognitive function

- Ventral tegmental area

- Prefrontal cortex

Mesolimbic system

Major dopamine pathway responsible for reward & pleasure

- Ventral tegmental area

- Nucleus accumbens

- Amygdala

- Hippocampus

Nigrostriatal system

Major dopamine pathway responsible for movement - Substantia nigra

- Neostriatum

Tuberoinfundibular pathway

Major dopamine pathway responsible for prolactin production

- Arcuate nucleus

- Hypothalamus

- Median eminence

Dopamine produced in...

Substantia nigra & Ventral tegmental area

Dopamine receptors

5 types: D1, D2, D3, D4, D5

- Only metabotropic receptors!

D1 & D5: Gs Excitatory

D2, D3, D4: Gi Inhibitory

Norepinephrine is produced in the...

Locus coeruleus

Norepinephrine receptors...

Alpha, beta 1, alpha 2

Beta 1 receptor

- Norepinephrine

- Gs

Alpha 1 receptor

- Only postsynaptic

- Gq

Alpha 2 receptor

- Autoreceptor

- Gi

- Both pre and post synaptic

Autoreceptors are...

Gi receptors on the same membrane the signal is produced

Serontonin

AKA 5-hydroxytryptamine (5-HT), Indolamine

Tryptophan

Starting molecule in production of serotonin

Tryptophan hydroxylase

Enzyme that converts tryptophan to 5-HTP

- Rate limiting

- Adds OH group

5-HTP decarboxylase

Enzyme that converts 5-HTP to 5-HT (serotonin)

- Removes COOH group

Serotonin produced in...

Raphe nuclei, travels everywhere in the brain, but is in higher concentration in the brain stem (epinephrine as well)

Serotonin receptors

5HT1A:

- Autoreceptor (pre & post)

- Gi

5HT1B and 5HT1D:

- presynaptic

- Gi

5HT2A-2C:

- Gq

5HT4:

- Gs

5HT3:

- Ionotropic

Fluoxetine (Prozac)

Drug that inhibits re-uptake of 5-HT, increases serotonin

Fenfluramine

Drug that stimulates release of 5-HT, appetite suppressant

LSD

Drug that stimulates 5HT2A receptors, hallucinations

MDMA (ecstasy)

Serotonin transmitters run in reverse, release serotonin & norepinephrine, excitatory effect

Glutamate receptors (ionotropic)

NMDA

- controls Ca2+ channel that gets blocked by Mg+ ions

- controlled very tightly

- ligand and voltage dependent

AMPA

- controls Na+ channel

- Fastest (ligand gated, some voltage as well)

Kainate receptor

- controls Na+ channel, stimulated by kainic acid

mGluR

Metabotropic glutamate receptors, 8 types separated into 3 groups

Group 1

- mGlu1

-mGlu5

Dopaminergic, Gq

Group 2

- mGlu2

- mGlu3

Gi

Group 3

- mGlu4

- mGlu6,7,8

AP5

Drug that blocks glutamate binding site on NMDA receptors

PCP

Drug that binds with PCP binding site of the NMDA receptor, indirect antagonist

GABAa & GABAc receptors

- Inhibitory

- Ionotropic receptors

GABAa- everywhere in CNS

GABAc- more localized to retina

GABAb receptors

- Metabotropic (G protein-coupled)

Non-Classical neurotransmitters...

- Peptides

- Lipids

- Nucleosides

- Soluble gases

Non-classical neurotransmitters are synthesized in the _____ rather than the _______

Soma, terminal

Primary excitatory & inhibitory transmitters in the brain

glutamate (excitatory) and GABA (inhibitory)