Distribution of several gut neuropeptides and their effects on motor activity in muscularis mucosae of guinea-pig proximal colon

The distribution of peptide-containing nerve fibers and the effect of their neuropeptides on motor activity were studied in the muscularis mucosae of the guinea-pig proximal colon. In the immunohistochemical study, it was shown that the tachykinin (TK)-containing nerve fibers densely innervated the muscularis mucosae. In the superfusion study, three kinds of TKs, i.e., neurokinin A (NK-A), neurokinin B (NK-B) or substance P (SP), enhanced the spontaneous activity on the strips of muscularis mucosae with a tetrodotoxin (TTX)-insensitive manner. Their potency was in the rank order of NK-A > SP. This suggests that the muscle has a predominant NK2 receptor. Calcitonin gene-related peptide (CGRP)-immunoreactive fibers were commonly observed in the muscle. CGRP induced a potent inhibition on spontaneous activity and a concentration-dependent inhibition on the NK-A-elicited excitation in the presence of TTX, indicating its direct effect on the receptor in the muscle. On the other had, gastrin releasing peptide (GRP), galanin, neuropeptide Y or somatostatin were more or less immunopositive in nerve fibers, but they had no effect on the motility of the muscle except that GRP sometimes showed a faint increase in spontaneous activity. Neither methionine-enkephalin nor gastrin-17/cholecystokinin was immunoreactive and had any effect on the muscle. These neuropeptides other than TKs and CGRP do not seem to be neuromediators of motor activity of muscularis mucosae. The results suggest the possibility that TK-, especially NK-A- and CGRP-containing neurons, participate in the regulation of motor activity of the muscularis mucosae in the guinea-pig proximal colon.