NITRIC-OXIDE MEDIATES CERULEIN-INDUCED RELAXATION OF CANINE SPHINCTEROF ODDI

This study evaluates the hypothesis that cerulein relaxes the sphincte r of Oddi (SO) via nitric oxide (NO). The spontaneous motility and the response to cerulein on the canine SO were recorded using a constant- perfusion technique. N-G-L-arginine-methyl-ester (L-NAME) increased th e spontaneous motility and dose-dependently reduced the cerulein-induc ed inhibitory response of the SO. After treatment with L-NAME at highe r doses, cerulein induced an excitatory response. This effect was reve rsed by treatment with excess L-arginine. Similar results were obtaine d using cholecystokinin octapeptide in place of cerulein. In separate studies, cerulein generated increases in intracellular cAMP and cGMP l evels in the SO. This indicates that the intracellular mechanism media ting cerulein-induced relaxation involves the production of cAMP and c GMP. On the other hand, treatment with L-NAME absorbed the increase in cAMP and cGMP levels by cerulein. These studies demonstrate that ceru lein relaxes the canine SO mainly via NO, increasing intracellular cAM P and cGMP levels.