Serotonin: Its Role and Receptors in Enteric Neurotransmission

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Abstract
The gastrointestinal tract represents the largest depot of 5-hydroxytryptamine (5-HT) in the body (Erspamer, 1966). Within the gut, 5-HT is found both in enteroendocrine (EC) cells in the epithelium of the mucosa (Erspamer, 1966; Nilsson et al., 1985) and in neurons of the myenteric plexus (Costa et al., 1982; Gershon, 1982; Furness and Costa, 1987). The 5-HT-containing EC cells develop from embryonic endoderm, while the neurons develop from the neural crest (Le Douarin, 1982). Neither the roles played in gastrointestinal physiology by EC cell 5-HT nor those of serotonergic neurons have been ascertained; however, 5-HT is probably involved in the regulation of gastrointestinal motility. A variety of stimuli have been reported to release 5-HT from EC cells, including mucosal pressure (Bülbring and Lin, 1958; Bülbring and Crema, 1959) and activation of splanchnic or vagus nerves (Ahlman et al., 1976; Ahlman and Dahlström, 1983; Gronstad et al., 1985). Pressure applied to the mucosa of the gut also initiates the peristaltic reflex, a response that can also be elicited by mucosal but not serosal application of 5-HT (Bülbring and Crema, 1958; Bülbring and Lin, 1958). It has thus been proposed that EC cells are pressure receptors and that they release 5-HT, not into the lumen of the bowel, but to the lamina propria, where intrinsic primary afferent nerve fibers that are sensitive to 5-HT are located. If this hypothesis is correct, then enteric neuronal 5-HT receptors would have to be present in the lamina propria. Enteric serotonergic neurons are interneurons, innervating serotonergic and other ganglion cells in both enteric plexuses (Dreyfus et al., 1977; Furness and Costa, 1982, 1987; Gershon and Sherman, 1987). Enteric neuronal 5-HT receptors, therefore, should also be found with enteric ganglia.