A NITRIC-OXIDE AND PROSTAGLANDIN-DEPENDENT COMPONENT OF NANC OFF-CONTRACTIONS IN CAT COLON

A nitric oxide and prostaglandin-dependent component of NANC off-contr actions in cat colon. Am. J. Physiol. 266 (Gastrointest. Liver Physiol . 29): G40-G47, 1994.-The actions of NO synthase inhibitors and indome thacin, a cyclooxygenase inhibitor, on the nonadrenergic noncholinergi c (NANC) mechanical responses of cat distal colon were studied in vitr o using muscle strips orientated in the axis of the longitudinal muscl e layer with pelvic nerves attached. Electrical field stimulation (EFS ) or pelvic nerve stimulation (PNS) caused inhibition of spontaneous c ontractions followed by off-contractions, Indomethacin (10-30 mu M) ca used concentration-dependent reductions in amplitude and duration of E FS- and PNS-evoked off-contractions but not latency. The NO synthase i nhibitors, N omega-nitro-L-arginine (L-NNA), N omega-nitro-L-arginine methyl ester (L-NAME) and N-G-monomethyl-L-arginine (L-NMMA) (each at 100 mu M) significantly reduced latency, amplitude, and duration of of f-contractions evoked by EFS and PNS. This inhibition was partially re versed by L-arginine (120 omega M) but not by D-arginine. Incubation o f colonic strips with alpha-chymotrypsin (2 U/ml) decreased latency, a mplitude, and duration of NANC off-contractions. L-NNA reduced amplitu de, duration, and latency of off-contractions in preparations pretreat ed with generator of a-chymotrypsin. Hydroquinone (10-30 omega M), a, superoxide anions, caused significant depression of amplitude, duratio n, and latency of off-contractions which was completely reversed by su peroxide dismutase (200 U/ml). These data suggest that the components of NANC off-contractions evoked by EFS and PNS involve peptides, NO, a nd prostaglandins.