NONADRENERGIC, NONCHOLINERGIC INHIBITORY JUNCTION POTENTIALS IN RAT PROXIMAL COLON - ROLE OF NITRIC-OXIDE

Using a single sucrose gap apparatus, experiments were performed to de termine the involvement of nitric oxide (NO) in the generation of nona drenergic, noncholinergic (NANC) inhibitory junction potentials in cir cular muscle of rat proximal colon. Inhibitors of NO synthase, N-omega -nitro-L-arginine and its methyl ester, reduced the amplitude of the e lectrically evoked inhibitory junction potentials, without affecting m embrane resting potential. Such an effect was stereospecific and it wa s prevented by L-arginine but not by D-arginine. Sodium nitroprusside induced a tetrodotoxin-resistant hyperpolarization, which was not affe cted by NO synthase inhibitors. Apamin reduced sodium nitroprusside in duced hyperpolarization, as well as NANC inhibitory junction potential s, and alpha-chymotrypsin decreased the amplitude of electrical field stimulation evoked responses. Residual responses after NO synthase inh ibitors or after alpha-chymotrypsin were further reduced by pretreatme nt with alpha-chymotrypsin or NO synthase inhibitors, respectively. Th ese results suggest that, in rat colonic circular muscle, NO plays an important role in NANC inhibitory junction potential generation. Howev er, another mechanism, peptidergic in nature, is also involved.