C h a p t e r 3 4
Organization and Control of Neural Function
851
Acetylcholine and Cholinergic Receptors
Acetylcholine (ACh) is the preganglionic neurotransmit-
ter in autonomic ganglia of both the sympathetic and
parasympathetic nerve fibers as well as the postgangli-
onic neurotransmitter in parasympathetic nerve endings.
It also is released at sympathetic nerve endings that inner-
vate the sweat glands and cholinergic vasodilator fibers
found in skeletal muscle. Acetylcholine is synthesized in
cholinergic neurons from choline and acetyl coenzyme A
(acetyl CoA) by a single step reaction catalyzed by the bio-
synthetic enzyme choline acetyltransferase (Fig. 34-24A).
Once synthesized, ACh is transported from the cytoplasm
into vesicles that are concentrated on the inner surface of
the presynaptic neuron. Activation of the postsynaptic
receptors occurs with action potential-mediated release
of ACh from the presynaptic vesicles. Following disso-
ciation from the postsynaptic receptors, ACh is rapidly
hydrolyzed by the enzyme acetylcholinesterase (AChE)
into acetate and choline in the synaptic cleft. The cho-
line molecule is transported back into the nerve ending,
where it is used again in the synthesis of ACh.
Cell membrane receptors that respond to acetylcholine
are called
cholinergic receptors
. There are two types of
cholinergic receptors: nicotinic and muscarinic. Nicotinic
ACh receptors are of two types: muscle type receptor (N
M
or N
1
) and neuronal type receptor (N
N
or N
2
). N
M
recep-
tor is located in the neuromuscular junction, which causes
the contraction of skeletal muscles by way of end-plate
potential. N
N
receptor causes depolarization in autonomic
ganglia resulting in postganglionic impulse. Some skeletal
muscle relaxants, such as succinylcholine and tubocura-
rine, can be used to induce muscle relaxation and short-
termparalysis in anesthesia by blocking N
M
receptors at the
neuromuscular junction. Muscarinic acetylcholine recep-
tors are present on the innervational targets of postgangli-
onic fibers of the parasympathetic nervous system and the
sweat glands, which are innervated by the sympathetic ner-
vous system. The drug atropine is a competitive antagonist
for the muscarinic acetylcholine receptor that prevents the
action of acetylcholine at excitatory and inhibitory mus-
carinic receptor sites. Because it is a muscarinic-blocking
drug, it exerts little effect at nicotinic receptor sites.
Mitochondrion
Presynaptic
terminal
Acetylcholinesterase
Acetyl-CoA
Choline
Acetylcholine (ACh)
+
Cholinergic
receptor
ACh
ACh
ACh
ACh
ACh
Choline
Acetate
Postsynaptic cell
A
Presynaptic
terminal
Mitochondrion
Postsynaptic cell
Tyrosine
L
-dopa
Dopamine
Synaptic
cleft
Monamine
oxidase (MAO)
COMT
NE
NE
NE
NE
NE
O-methylated
metabolites
Deaminated
metabolites
Adrenergic
receptor
α
2
-Adrenergic
receptor
Reuptake
B
FIGURE 34-24.
Schematic illustration of
(A)
parasympathetic cholinergic and
(B)
sympathetic
noradrenergic neurotransmitter synthesis, release, receptor binding, neurotransmitter degradation, and
metabolite transport back into the presynaptic neuron (acetylcholine) and reuptake (norepinephrine).
COMT, catechol-O-methyltransferase; NE, norepinephrine; ChAT, Choline acetyltransferase.
