Chapter 11
Fundamentals of the Nervous System and Nervous Tissue
415
11
Table 11.3
Neurotransmitters and Neuromodulators
NEUROTRANSMITTER
FUNCTIONAL CLASSES
SITES WHERE SECRETED
COMMENTS
Acetylcholine (ACh)
At
nicotinic ACh recep-
tors
(on skeletal muscles,
autonomic ganglia, and
in the CNS)
At
muscarinic ACh recep-
tors
(on visceral effectors
and in the CNS)
Excitatory
Direct action
Excitatory or inhibitory
depending on subtype of
muscarinic receptor
Indirect action via second
messengers
CNS: widespread throughout
cerebral cortex, hippocampus,
and brain stem
PNS: all neuromuscular
junctions with skeletal muscle;
some autonomic motor
endings (all preganglionic and
parasympathetic postganglionic
fibers)
Effects prolonged when AChE
blocked by nerve gas or organo-
phosphate insecticides (malathion),
leading to tetanic muscle spasms.
Release inhibited by botulinum toxin;
binding to nicotinic ACh receptors in-
hibited by curare (a muscle paralytic
agent) and to muscarinic ACh recep-
tors by atropine. ACh levels decrease
in certain brain areas in Alzheimer’s
disease; nicotinic ACh receptors
destroyed in myasthenia gravis. Bind-
ing of nicotine to nicotinic receptors
in the brain enhances dopamine
release, which may account for the
behavioral effects of nicotine in
smokers.
Biogenic Amines
Norepinephrine (NE)
Excitatory or inhibitory
depending on receptor type
bound
Indirect action via second
messengers
CNS: brain stem, particularly
in the locus coeruleus of the
midbrain; limbic system; some
areas of cerebral cortex
PNS: main neurotransmitter of
postganglionic neurons in the
sympathetic nervous system
A “feel good” neurotransmitter.
Release enhanced by amphetamines;
removal from synapse blocked
by tricyclic antidepressants
[amitriptyline (Elavil) and others]
and cocaine. Brain levels reduced
by reserpine (an antihypertensive
drug), leading to depression.
Dopamine
Excitatory or inhibitory
depending on the receptor type
bound
Indirect action via second
messengers
CNS: substantia nigra of
midbrain; hypothalamus; the
principal neurotransmitter of
indirect motor pathways
PNS: some sympathetic ganglia
A “feel good” neurotransmitter.
Release enhanced by
L
-dopa and
amphetamines; reuptake blocked
by cocaine. Deficient in Parkinson’s
disease; dopamine neurotransmission
increases in schizophrenia.
Serotonin (5-HT)
Mainly inhibitory
Indirect action via second
messengers; direct action at
5-HT
3
receptors
CNS: brain stem, especially
midbrain; hypothalamus; limbic
system; cerebellum; pineal gland;
spinal cord
Plays a role in sleep, appetite,
nausea, migraine headaches, and
regulating mood. Drugs that block
its uptake [fluoxetine (Prozac)]
relieve anxiety and depression.
Activity blocked by LSD and
enhanced by ecstasy (MDMA).
Histamine
Excitatory or inhibitory
depending on receptor type
bound
Indirect action via second
messengers
CNS: hypothalamus
Involved in wakefulness, appetite
control, and learning and memory.
Also a paracrine (local signal)
released from stomach (causes acid
secretion) and connective tissue
mast cells (mediates inflammation
and vasodilation).
Amino Acids
GABA (
g
-aminobutyric acid)
Generally inhibitory
Direct and indirect actions via
second messengers
CNS: cerebral cortex,
hypothalamus, Purkinje cells of
cerebellum, spinal cord, granule
cells of olfactory bulb, retina
Principal inhibitory neurotransmitter
in the brain; important in
presynaptic inhibition at axoaxonal
synapses. Inhibitory effects
augmented by alcohol, antianxiety
drugs of the benzodiazepine class
(e.g., Valium), and barbiturates,
impairing motor coordination.
Substances that block its synthesis,
release, or action induce convulsions.
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