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SECTION III
Central & Peripheral Neurophysiology
The neurons that are cholinergic (ie, release acetylcholine) are
(1) all preganglionic neurons, (2) all parasympathetic postgan-
glionic neurons, (3) sympathetic postganglionic neurons that
innervate sweat glands, and (4) sympathetic postganglionic
neurons that end on blood vessels in some skeletal muscles and
produce vasodilation when stimulated (sympathetic vasodilator
nerves). The remaining sympathetic postganglionic neurons
are noradrenergic (ie, release norepinephrine). The adrenal me-
dulla is essentially a sympathetic ganglion in which the postgan-
glionic cells have lost their axons and secrete norepinephrine
and epinephrine directly into the bloodstream. The cholinergic
preganglionic neurons to these cells have consequently become
the secretomotor nerve supply of this gland.
Transmission in autonomic ganglia is mediated primarily by
N
2
nicotinic cholinergic receptors that are blocked by hexame-
thonium. This is in contrast to the N
1
nicotinic cholinergic
receptors at the neuromuscular junction, which are blocked by
D-tubocurare. The release of acetylcholine from postganglionic
fibers acts on muscarinic receptors, which are blocked by atro-
pine. The release of norepinephrine from sympathetic postgan-
glionic fibers acts on
α
1
,
β
1
, or
β
2
adrenoreceptors, depending
on the target organ. Table 17–1 shows the types of receptors at
various junctions within the autonomic nervous system.
In addition to these “classical neurotransmitters,” some auto-
nomic fibers also release neuropeptides. Figure 17–4 shows
some examples for sympathetic postganglionic fibers. The small
granulated vesicles in postganglionic noradrenergic neurons
contain ATP and norepinephrine, and the large granulated vesi-
cles contain neuropeptide Y. There is evidence that low-fre-
quency stimulation promotes release of ATP, whereas high-
frequency stimulation causes release of neuropeptide Y. The vis-
cera contains purinergic receptors, and evidence is accumulating
that ATP is a mediator in the autonomic nervous system along
with norepinephrine. However, its exact role is unsettled.
Acetylcholine does not usually circulate in the blood, and the
effects of localized cholinergic discharge are generally discrete and
of short duration because of the high concentration of acetylcho-
linesterase at cholinergic nerve endings. Norepinephrine spreads
farther and has a more prolonged action than acetylcholine. Nor-
epinephrine, epinephrine, and dopamine are all found in plasma.
The epinephrine and some of the dopamine come from the adre-
nal medulla, but most of the norepinephrine diffuses into the
bloodstream from noradrenergic nerve endings. Metabolites of
norepinephrine and dopamine also enter the circulation, some
from the sympathetic nerve endings and some from smooth mus-
cle cells (Figure 17–5). It is worth noting that even when
monoamine oxidase (MAO) and catechol-
O
-methyltransferase
(COMT) are both inhibited, the metabolism of norepinephrine is
still rapid. However, inhibition of reuptake prolongs its half-life.
TRANSMISSION IN
SYMPATHETIC GANGLIA
At least in experimental animals, the responses produced in
postganglionic neurons by stimulation of their preganglionic
innervation include both a rapid depolarization
(fast excitatory
postsynaptic potential [EPSP])
that generates action potentials
and a prolonged excitatory postsynaptic potential
(slow EPSP).
The slow response apparently modulates and regulates trans-
mission through the sympathetic ganglia. As just described, the
initial depolarization is produced by acetylcholine via the N
2
nicotinic receptor. The slow EPSP is produced by acetylcholine
acting on a muscarinic receptor on the membrane of the post-
ganglionic neuron.
The junctions in the peripheral autonomic motor pathways are
a logical site for pharmacologic manipulation of visceral func-
tion. The transmitter agents are synthesized, stored in the nerve
endings, and released near the neurons, muscle cells, or gland
cells on which they act. They bind to receptors on these cells, thus
initiating their characteristic actions, and they are then removed
from the area by reuptake or metabolism. Each of these steps can
be stimulated or inhibited, with predictable consequences.
Some of the drugs and toxins that affect the activity of the
autonomic nervous system and the mechanisms by which they
produce their effects are listed in Table 17–2. Compounds with
muscarinic actions include congeners of acetylcholine and
drugs that inhibit acetylcholinesterase. Among the latter are the
insecticide parathion and diisopropyl fluorophosphate (DFP), a
component of the so-called nerve gases, which kill by produc-
ing massive inhibition of acetylcholinesterase.RESPONSES OF EFFECTOR
ORGANS TO AUTONOMIC
NERVE IMPULSES
GENERAL PRINCIPLES
The effects of stimulation of the noradrenergic and choliner-
gic postganglionic nerve fibers are indicated in Figure 17–3
and Table 17–1. These findings point out another difference
between the ANS and the somatomotor nervous system. The
release of acetylcholine by
α
-motor neurons only leads to con-
traction of skeletal muscles. In contrast, release of acetylcho-
line onto smooth muscle of some organs leads to contraction
(eg, walls of the gastrointestinal tract) while release onto other
organs leads to relaxation (eg, sphincters in the gastrointesti-
nal tract). The only way to relax a skeletal muscle is to inhibit
the discharges of the
α
-motor neurons; but for some targets
innervated by the ANS, one can shift from contraction to re-
laxation by switching from activation of the parasympathetic
nervous system to activation of the sympathetic nervous sys-
tem. This is the case for the many organs which receive dual
innervation with antagonistic effects, including the digestive
tract, airways, and urinary bladder. The heart is another exam-
ple of an organ with dual antagonistic control. Stimulation of
sympathetic nerves increases heart rate, and stimulation of
parasympathetic nerves decreases heart rate.
In other cases, the effects of sympathetic and parasympa-
thetic activation can be considered complementary. An example