Porth's Essentials of Pathophysiology, 4e

851

Organization and Control of Neural Function

C h a p t e r 3 4

Presynaptic terminal

Tyrosine

L -dopa

Monamine oxidase (MAO)

Dopamine

Mitochondrion

NE

Presynaptic terminal

NE

Acetyl-CoA Choline +

NE

Reuptake

α 2

-Adrenergic receptor

Synaptic cleft

NE

Acetylcholine (ACh)

Mitochondrion

ACh

ACh

ACh

ACh

Choline

Adrenergic receptor

Postsynaptic cell

NE

COMT

ACh

Acetylcholinesterase

Cholinergic receptor

Acetate

O-methylated metabolites

Deaminated metabolites

A

Postsynaptic cell 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.

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.