cyclic-gmp and Biliary-Dyskinesia

This study evaluates the hypothesis that cerulein relaxes the sphincter 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 the spontaneous motility and dose-dependently reduced the cerulein-induced inhibitory response of the SO. After treatment with L-NAME at higher doses, cerulein induced an excitatory response. This effect was reversed by treatment with excess L-arginine. Similar results were obtained using cholecystokinin octapeptide in place of cerulein. In separate studies, cerulein generated increases in intracellular cAMP and cGMP levels in the SO. This indicates that the intracellular mechanism mediating cerulein-induced relaxation involves the production of cAMP and cGMP. On the other hand, treatment with L-NAME absorbed the increase in cAMP and cGMP levels by cerulein. These studies demonstrate that cerulein relaxes the canine SO mainly via NO, increasing intracellular cAMP and cGMP levels.

Topics: Animals; Biliary Dyskinesia; Ceruletide; Cyclic AMP; Cyclic GMP; Dogs; Enzyme Inhibitors; Female; Gastrointestinal Agents; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Second Messenger Systems; Sphincter of Oddi

The paper concerns studying the participation of cyclic nucleotides in the mechanisms of action of cholecystokinin on gallbladder function in man. Cyclic nucleosides (cAMP and cGMP) were identified by radioimmunoassay in the duodenal contents obtained from men in response to intravenous injection of cholecystokinin. The data obtained suggest that the action of cholecystokinin on gallbladder function in man is mediated via cGMP, whereas cAMP is not implicated in the effect of of cholecystokinin on gallbladder function in man. Disturbances in cyclic nucleotide systems may be viewed in the light of the evidence obtained as a possible pathogenetic factor in the development of gallbladder dyskinesia.

Topics: Bile; Biliary Dyskinesia; Cholecystokinin; Cyclic AMP; Cyclic GMP; Fatty Liver; Humans; Liver; Time Factors