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
Alzheimer’s disease
loss of ACh neurons in
the basal nucleus of Meynert
Aricept—ACh 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)
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
a
b c
d
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
Hebb’s 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
gonadotropningrowth hormonereleasing hormone releasing hormone
luteinizing
hormone
calcitonin
insulin
glucagon
vasopressin
angiotensin II
thyrotropinreleasing hormone
vasoactive
intestinal peptide
Soluble Gases
Nitric Oxide (NO)
Carbon Monoxide