Neurotransmitters

Neurotransmitter
Criteria
1. Identity

Substance must be found in neu

Neurotransmitter
Criteria
1. Identity
2. Synthesis

Cell has precursors and enzymes

necessary for synthesis

Neurotransmitter
Criteria
1. Identity
2. Synthesis
3. Release

Must be released from terminals

(collect substance from cleft
after nerve stimulation)

Neurotransmitter
Criteria
1.
2.
3.
4.

Identity
Synthesis
Release
Receptors

Cross desensitization between

substance and suspected n.t.

Blockade of n.t. action by rece

antagonists

Applicaton of suspected n.t.

mimics action of nerve stimul

Neurotransmitter
Criteria
1.
2.
3.
4.
5.

Identity
Synthesis
Release
Receptors
Inactivation
Inactivation mechanism
enzymatic degradation
reuptake

Neurotransmitter
Criteria
1.
2.
3.
4.
5.
6.

Identity
Synthesis
Release
Receptors
Inactivation
Pharmacology

Same effect on ion channels;

p.s.p.s have same reversal pote

Same effect on membrane resista

and potential

Applied substances must be effec

in physiological concentrations
Inhibition of degrading enzyme
prolongs action of both

Neurotransmitter
Criteria
1.
2.
3.
4.
5.
6.

Identity
Synthesis
Release
Receptors
Inactivation
Pharmacology

Acetylcholine Synthesis
Choline Acetyltransferase (ChAT)
Acetyl CoA + Choline

Acetylcholine + CoA

+ CoA

Degradation
Acetylcholine Esterase (AchE)
Acetylcholine

Choline + Acetate

Chemicals that Act

on ACh Systems
black widow spider venom
stimulates release of ACh

botulinum toxin
blocks release of ACh

curare
blocks ACh nicotinic receptors

insecticides
AChE inhibitors
atropine as antidote
blocks muscarinic receptors

Clinical Aspects
of ACh Systems
Alzheimers disease
loss of ACh neurons in
the basal nucleus of Meynert
AriceptACh agonist

Monoamines
single amine (NH2) group
Catecholamines (CAs)
dopamine (DA)
norepinephrine (NE, noradrenaline)
epinephrine (EPI, adrenaline)

Indoleamines
serotonin (5-hydroxy tryptamine, 5-HT)

Catecholamine synthesis

Serotonin synthesis

Dopamine Systems

Norepinephrine Systems

SystemsSerotonin

Characteristics of
Monoaminergic Systems
Diffuse distribution of targets
Fine, unmyelinated axons
Metabotropic synapses

Functions of
Monaminergic Systems
State phenomena
sleep and arousal
hunger
mood

Amino Acid Transmitters

Excitatory Amino Acid
Glutamic Acid, or Glutamate

Inhibitory Amino Acids

Gamma Aminobutyric Acid (GABA)
Glutamic Acid
Decarboxylase (GAD)
Glutamic Acid
Glycine

GABA

Glutamate Receptor Subtypes

NMDA receptor binding sites

http://www.sumanasinc.com/webcontent/anisamples/neurobiology/receptors.htm

Glutamate
non-NMDA receptors
Na+ channels
open
removes
blockade
depolarization

NMDA receptors
Ca2+ channels
open
(Mg2+ blockade)
Ca2+ enters
when Mg2+
is removed

postsynaptic
effects
(learning)

reinstates blockade

Ca2+dependent
K+ channels
open

repolarization

a. Non-NMDA Na+ channels open, Na+

enters and depolarizes membrane
b. Mg2+ blockade of NMDA Ca2+ channels
removed by membrane depolarization;
Ca2+ enters
c. Ca2+ dependent K+ channels open;
membrane repolarized
d. Mg2+ blockade reinstated

b c

GABA receptor binding sites

Peptide
Neurotransmitters
(Often serve hormonal functions
as well)
Substance P (P for Peptide)
Principal somatosensory transmitter
First peptide transmitter discovered
Gut hormones
e.g. angiotensin
neuropeptide Y
cholecystokinin
Releasing factors for hormones
e.g. tryrotropin releasing hormone
somatotrophin, somatostatin
corticotropin
Opiates
Enkephalins, Endorphins

Diffusible Gases
Nitric Oxide (NO)
Nitric Oxide
Synthase (NOS)
Arginine

NO + Citrulline

Carbon Monoxide (CO)

Heme Oxygenase
Heme

CO + biliverdin

Functions of
Diffusible Gas
Neurotransmitters
regulate blood flow
cerebral
peripheral (e.g. penis)
retrograde messenger
Hebbs postulate of learning

Summary of Neurotransmitters
Small Molecule Neurotransmitter Substances
Acetylcholine (ACh)
Serotonin (5-HT)

Dopamine (DA)
Histamine

Norepinephrine (NE)
Epinephrine

Amino Acids
Gamma-aminobutyric
acid (GABA)

Glycine

Glutamate

Aspartate

Neuroactive Peptides - partial list

bradykinin
cholecystokinin
gastrin
secretin
oxytocin

beta-endorphin
enkephalin
substance P
somatostatin
prolactin

bombesin
dynorphin
neurotensin
motilin
thyrotropin

sleep peptides

galanin

neuropeptide Y

gonadotropnin- growth hormonereleasing hormone releasing hormone

luteinizing
hormone

calcitonin
insulin
glucagon
vasopressin
angiotensin II
thyrotropinreleasing hormone
vasoactive
intestinal peptide

Soluble Gases
Nitric Oxide (NO)

Carbon Monoxide