NONADRENERGIC, NONCHOLINERGIC INHIBITION AND REBOUND EXCITATION IN CANINE COLON DEPEND ON NITRIC-OXIDE

Nonadrenergic, noncholinergic (NANC) nerves regulate slow waves along the submucosal border of the canine proximal colon. Experiments were performed to determine the role of nitric oxide (NO) in NANC responses. NANC responses are characterized by hyperpolarization and reduction in slow-wave amplitude and duration during the period of stimulation. This is followed by a "rebound" excitation (increase in amplitude and duration) of the slow wave immediately after the stimulus. These responses were blocked by L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase and by tetrodotoxin (TTX). Exogenous NO mimicked NANC responses, including the poststimulus rebound excitation. Responses to NO were unaffected by L-NAME or TTX. Responses to NANC nerve stimulation and NO were blocked by oxyhemoglobin but not by methemoglobin. Rebound excitation was reduced by pretreatment with indomethacin, suggesting that an eicosanoid may mediate this phase of NANC responses. Taken together, these data suggest that NO mediates NANC nerve responses in the proximal colon. NO appears to directly cause the inhibitory response, but the rebound response may depend on release of an eicosanoid.