DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

176 ganglia, the ratio of preganglionic axons to ganglion
cells may be 1:20 or more. This organization permits a
diffuse discharge of the sympathetic system. In addition,
synaptic innervation overlaps, so one ganglion cell
may be supplied by several preganglionic fibers.
The parasympathetic system, in contrast, has
terminal ganglia very near or within the organs innervated
and thus is more circumscribed in its influences.
In some organs, a 1:1 relationship between the number
of preganglionic and postganglionic fibers has been
suggested, but the ratio of preganglionic vagal fibers to
ganglion cells in the myenteric plexus has been
estimated as 1:8000. Hence this distinction between the
two systems does not apply to all sites.
The cell bodies of somatic motor neurons reside in
the ventral horn of the spinal cord; the axon divides into
many branches, each of which innervates a single muscle
fiber, so more than 100 muscle fibers may be supplied by
one motor neuron to form a motor unit. At each neuromuscular
junction, the axonal terminal loses its myelin
sheath and forms a terminal arborization that lies in apposition
to a specialized surface of the muscle membrane,
termed the motor end plate. Mitochondria and a collection
of synaptic vesicles are concentrated at the nerve terminal.
Through trophic influences of the nerve, those cell
nuclei in the multinucleated skeletal muscle cell lying in
close apposition to the synapse acquire the capacity to
activate specific genes that express synapse-localized proteins
(Sanes and Lichtman, 1999). Differences among
somatic motor, sympathetic and parasympathetic nerves
are shown schematically in Figure 8–2.
SECTION II
NEUROPHARMACOLOGY
Details of Innervation. The terminations of the postganglionic autonomic
fibers in smooth muscle and glands form a rich plexus, or terminal
reticulum. The terminal reticulum (sometimes called the autonomic
ground plexus) consists of the final ramifications of the postganglionic
sympathetic, parasympathetic, and visceral afferent fibers, all of which
are enclosed within a frequently interrupted sheath of satellite or
Schwann cells. At these interruptions, varicosities packed with vesicles
are seen in the efferent fibers. Such varicosities occur repeatedly but at
variable distances along the course of the ramifications of the axon.
“Protoplasmic bridges” occur between the smooth muscle fibers
themselves at points of contact between their plasma membranes. They
are believed to permit the direct conduction of impulses from cell to cell
without the need for chemical transmission. These structures have been
termed nexuses, or tight junctions, and they enable the smooth muscle
fibers to function as a syncytial unit.
Sympathetic ganglia are extremely complex anatomically and
pharmacologically (see Chapter 11). The preganglionic fibers lose
their myelin sheaths and divide repeatedly into a vast number of end
fibers with diameters ranging from 0.1-0.3 μm; except at points of
synaptic contact, they retain their satellite cell sheaths. The vast
majority of synapses are axodendritic. Apparently, a given axonal
terminal may synapse with one or more dendritic processes.
Responses of Effector Organs to Autonomic Nerve
Impulses. From the responses of the various effector
organs to autonomic nerve impulses and the knowledge
of the intrinsic autonomic tone, one can predict the
actions of drugs that mimic or inhibit the actions of
these nerves. In most instances, the sympathetic and
parasympathetic neurotransmitters can be viewed as
physiological or functional antagonists. If one
neurotransmitter inhibits a certain function, the other
usually augments that function. Most viscera are innervated
by both divisions of the autonomic nervous system,
and the level of activity at any moment represents
the integration of influences of the two components.
Despite the conventional concept of antagonism
between the two portions of the autonomic nervous
system, their activities on specific structures may be
either discrete and independent or integrated and interdependent.
For example, the effects of sympathetic and
parasympathetic stimulation of the heart and the iris
show a pattern of functional antagonism in controlling
heart rate and pupillary aperture, respectively, whereas
their actions on male sexual organs are complementary
and are integrated to promote sexual function. The control
of peripheral vascular resistance is primarily, but
not exclusively, due to sympathetic control of arteriolar
resistance. The effects of stimulating the sympathetic
and parasympathetic nerves to various organs,
visceral structures, and effector cells are summarized
in Table 8–1.
General Functions of the Autonomic Nervous System.
The integrating action of the autonomic nervous system
(ANS) is of vital importance for the well-being of the
organism. In general, the ANS regulates the activities of
structures that are not under voluntary control and that
function below the level of consciousness. Thus, respiration,
circulation, digestion, body temperature, metabolism,
sweating, and the secretions of certain endocrine glands
are regulated, in part or entirely, by the autonomic nervous
system, making the ANS the primary regulator of the
constancy of the internal environment of the organism.
The sympathetic system and its associated adrenal
medulla are not essential to life in a controlled environment,
but the lack of sympatho-adrenal functions
becomes evident under circumstances of stress. Body
temperature cannot be regulated when environmental
temperature varies; the concentration of glucose in
blood does not rise in response to urgent need;
compensatory vascular responses to hemorrhage,
oxygen deprivation, excitement, and exercise are lacking;
resistance to fatigue is lessened; sympathetic