As noted in the previous editions of this book and other stan-dard texts, it has long been believed that, like the cranial nerve cholinergic system described earlier, the cholinergic nerves that innervate the pelvic organs (rectum, bladder, and reproduc-tive organs) are part of the parasympathetic nervous system. However, a recent study (see Espinoza-Medina reference at the end of this chapter) suggests that the preganglionic sacral fibers are actually derived from embryonic sympathetic precur-sor cells and that the postganglionic fibers innervated by them are therefore members of the sympathetic cholinergic class. This claim is based on several lines of evidence, as follows: (1) Cranial parasympathetic preganglionic neurons express the homeo-gene Phox2b and the transcription factors Tbx20, Tbx2, and Tbx3; thoracic sympathetic and sacral preganglionic neurons do not. Sacral preganglionic neurons do express transcription fac-tor Foxp1, which is not expressed by cranial neurons. (2) Cranial parasympathetic preganglionic fibers exit the CNS via dorsolat-eral exit points; the sympathetic and sacral preganglionic nerves exit the spinal cord via ventral root exits. (3) At an early stage of development, cranial preganglionic neurons express the vesicu-lar acetylcholine transporter (VAChT; VAT in Figure 6–3) but not nitric oxide synthase (NOS); sympathetic and sacral nerves at the same stage express NOS but not VAChT (even though they do express VAChT later in their development). These observa-tions require independent confirmation but constitute strong evidence in favor of changing the traditional “craniosacral” synonym for the parasympathetic nervous system to “cranial autonomic” nervous system.
Effects are thus slower in onset, and discharge of a single motor fiber often activates or inhibits many effector cells.
An important traditional classification of autonomic nerves is based on the primary transmitter molecules—acetylcholine or norepinephrine—released from their terminals and varicosities. A large number of peripheral ANS fibers synthesize and release acetylcholine; they are cholinergic fibers; that is, they work by releasing acetylcholine. As shown in Figure 6–1, these include all preganglionic efferent autonomic fibers and the somatic (nonautonomic) motor fibers to skeletal muscle as well. Thus, almost all efferent fibers leaving the CNS are cholinergic. In addition, most parasympathetic postganglionic and some sympathetic postganglionic fibers are cholinergic. A significant number of parasympathetic postganglionic neurons use nitric oxide or peptides as the primary transmitter or as cotransmitters.
Most postganglionic sympathetic fibers (Figure 6–1) release norepinephrine (also known as noradrenaline); they are noradrenergic (often called simply “adrenergic”) fibers; that is, they work by releasing norepinephrine (noradrenaline). As noted, some sympathetic fibers release acetylcholine. Dopamine is a very important transmitter in the CNS, and it may be released by some peripheral sympathetic fibers under certain circumstances. Adrenal medullary cells, which are embryologically analogous to post-ganglionic sympathetic neurons, release a mixture of epinephrine and norepinephrine. Finally, most autonomic nerves also release several cotransmitter substances (described in the following text), in addition to the primary transmitters just described.
Five key features of neurotransmitter function provide potential targets for pharmacologic therapy: synthesis, storage, release, termination of action of the transmitter, and receptor effects. These processes are discussed next.