The most important of the autonomic neurotransmitters are ACh and NE. ACh is synthesized at the terminals of axons and stored in presynaptic vesicles until it is released by the arrival of nerve impulses. ACh is released at the terminals of all preganglionic fibers (in both the sympathetic and parasympathetic ganglia), as well as at the terminals of all postganglionic parasympathetic and a few special postganglionic sympathetic fibers, mainly those subserving sweat glands. Of course, ACh is also the chemical transmitter of nerve impulses to the skeletal muscle fibers. Parasympathetic postganglionic function is mediated by two distinct types of ACh receptors: nicotinic and muscarinic, so named by Dale because the choline-induced responses were similar either to those of nicotine or to those of the alkaloid, muscarine. The postganglionic parasympathetic receptors are located within the innervated organ and are muscarinic; that is, they are antagonized by atropinic drugs. As already mentioned the receptors in ganglia, like those of skeletal muscle, are nicotinic; they are not blocked by atropine but are counteracted by other agents (e.g., tubocurarine).
It is likely that more than ACh is involved in nerve transmission at a ganglionic level. Many peptides— substance P, enkephalins, somatostatin, vasoactive intestinal peptide, adenosine triphosphate (ATP), and nitric oxide—have been identified in the autonomic ganglia, localizing in some cases to the same cell as ACh. (This negates “Dale’s principle,” or “law,” which stipulates that one neuron elaborates only one neurotransmitter, as outlined by Tansey.) Particular neuronal firing rates appear to cause the preferential release of one or another of these substances. Most of the neuropeptides exert their postsynaptic effects through the G-protein transduction system, which uses adenyl cyclase or phospholipase C as an intermediary. The neuropeptides act as modulators of neural transmission, although their exact function in many cases remains to be determined.
With two exceptions, postganglionic sympathetic fibers release only NE at their terminals. The sweat glands and some blood vessels in muscle are innervated by postganglionic sympathetic fibers, but their terminals, as mentioned, release ACh. The NE that is discharged into the synaptic space activates specific adrenergic receptors on the postsynaptic membrane of target cells.
Adrenergic receptors are of two types, classified originally by Ahlquist as alpha and beta. In general, the alpha receptors mediate vasoconstriction, relaxation of the gut, and dilatation of the pupil; beta receptors mediate vasodilatation, especially in muscles, relaxation of the bronchi, and an increased rate and contractility of the heart. Each of these receptors is subdivided further into two types. Alpha1 receptors are postsynaptic; alpha2 receptors are situated on the presynaptic membrane and, when stimulated, diminish the release of the transmitter. Beta1 receptors are, for all practical purposes, limited to the heart; their activation increases the heart rate and contractility. Beta2 receptors, when stimulated, relax the smooth muscle of the bronchi and of most other sites, including the blood vessels of skeletal muscle. A comprehensive account of neurohumoral transmission and receptor function can be found in the monograph by Cooper and colleagues.
Discussed in the following pages are the ways in which the two divisions of the autonomic nervous system, acting in conjunction with the endocrine glands, maintain the homeostasis of the organism. As stated earlier, the integration of these two systems is achieved primarily in the hypothalamus. In addition, the endocrine glands are influenced by circulating catecholamines, and some of them are innervated by adrenergic fibers. Chapter 26 discusses further these autonomic–endocrine relations.
Regulation of Blood Pressure