Atrial natriuretic factor stimulates exocrine pancreatic secretion in the rat through NPR-C receptors

SABBATINI M; VILLAGRA A; DAVIO CA; VATTA MS; FERNADEZ BE; BIANCIOTTI LG

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Año: 2003 vol. 285 p. 929 - 937

0193-1857

Increasing evidence supports the role ofatrial natriuretic factor (ANF) in the modulation of gastrointestinalphysiology. The effect of ANF on exocrine pancreaticsecretion and the possible receptors and pathways involvedwere studied in vivo. Anesthetized rats were preparedwith pancreatic duct cannulation, pyloric ligation, and bilediversion into the duodenum. ANF dose-dependently increasedpancreatic secretion of fluid and proteins and enhancedsecretin and CCK-evoked response. ANF decreasedchloride secretion and increased the pH of the pancreaticjuice. Neither cholinergic nor adrenergic blockade affectedANF-stimulated pancreatic secretion. Furthermore, ANF responsewas not mediated by the release of nitric oxide.ANF-evoked protein secretion was not inhibited by truncalvagotomy, atropine, or N-nitro-L-arginine methyl ester administration.The selective natriuretic peptide receptor-C(NPR-C) receptor agonist cANP-(4?23) mimicked ANF responsein a dose-dependent fashion. When the intracellularsignaling coupled to NPR-C receptors was investigated inisolated pancreatic acini, results showed that ANF did notmodify basal or forskolin-evoked cAMP formation, but itdose-dependently enhanced phosphoinositide hydrolysis,which was blocked by the selective PLC inhibitor U-73122.ANF stimulated exocrine pancreatic secretion in the rat, andits effect was not mediated by nitric oxide or parasympatheticor sympathetic activity. Furthermore, CCK and secretinappear not to be involved in ANF response. Presentfindings support that ANF exerts a stimulatory effect onpancreatic exocrine secretion mediated by NPR-C receptorscoupled to the phosphoinositide pathway.