Structural and functional aspects of acetylcholine peptide coexistence in the autonomic nervous system.

The present article is an attempt to briefly review acetylcholine and peptide coexistence in the ANS. For more detailed information the reader is referred to the book by Furness and Costa (1987) and books edited by Elfvin (1983) and Björklund et al. (1988). Acetylcholine is the "classical" transmitter substance between preganglionic and post-ganglionic neurons in both the sympathetic and parasympathetic nervous system but also between postganglionic parasympathetic neurons and effector cells. ENK and NT were early on shown to be present in preganglionic sympathetic neurons whereas SP and SOM have more recently been associated with these cells. Physiological experiments have shown that ENK may presynaptically inhibit cholinergic transmission in sympathetic ganglia. The cholinergic postganglionic parasympathetic neurons contain VIP/PHI. These peptides may be responsible for the atropine-resistant vasodilation seen after stimulation of parasympathetic nerves. In salivary glands VIP has been shown to potentiate the salivatory volume response to ACh. A number of postganglionic sympathetic neurons innervating exocrine sweat glands in the skin are also cholinergic. In addition to VIP/PHI, these neurons contain CGRP and probably also SP. The functional significance of acetylcholine coexisting with four vasodilatory peptides in this cell population is at present unclear. In the enteric ganglia the coexistence situation is very complex. Thus, in the myenteric plexus cholinergic SP-containing excitatory motor neurons seem to be present. In the myenteric plexus other cholinergic neurons may contain at least six different neuronal peptides. These latter neurons seem to be part of the peripheral intestino-intestinal reflex arc which is involved in regulation of gastrointestinal motility and mucosal functions. In the submucous plexus three populations of cholinergic neurons are present, one of which has secretomotor properties and contains CGRP, CCK, GAL, NPY and SOM. In vivo and in vitro studies have shown that developing sympathetic neurons can "change" the "classical" transmitter they-use and alter their neuropeptide expression. If dissociated sympathetic neurons are grown in cultures without any non-neuronal elements they differentiate into a noradrenergic phenotype. However, if the cultures also contain non-neuronal cells, both noradrenergic and cholinergic properties will develop. These changes may also by induced by a conditioned medium, containing a diffusible factor secreted from the non-neuronal cells. In conclusion, the present article underlines the complexity of the chemical neuroanatomy of the ANS and emphasizes the abundance of the peptides in both noradrenergic and cholinergic neurons. Although these peptides can be shown to exert a number of interesting effects in various experimental paradigms, much work is needed to define their exact role in nervous system function.