Neurotransmitters

Neurotransmitter Criteria
1. Identity
Substance must be found in neurons

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 receptor antagonists Applicaton of suspected n.t. mimics action of nerve stimulation

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 potentials Same effect on membrane resistance and potential Applied substances must be effective 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 NMDA receptors

Na+ channels open removes blockade depolarization

Ca2+ channels open (Mg2+ blockade)

Ca2+ enters when Mg2+ is removed

postsynaptic effects (learning)

Ca2+dependent K+ channels open

reinstates blockade

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 Aspartate Glutamate

Neuroactive Peptides - partial list

bradykinin cholecystokinin gastrin secretin oxytocin sleep peptides beta-endorphin enkephalin substance P somatostatin prolactin galanin bombesin dynorphin neurotensin motilin thyrotropin neuropeptide Y luteinizing hormone calcitonin insulin glucagon vasopressin angiotensin II thyrotropinreleasing hormone vasoactive intestinal peptide

gonadotropningrowth hormonereleasing hormone releasing hormone

Soluble Gases
Nitric Oxide (NO) Carbon Monoxide