THE SOMATOSTATIN RECEPTOR-ADENYLATE CYCLASE SYSTEM IN RAT PANCREATIC ACINAR MEMBRANES AFTER TEMPORARY PANCREATICOBILIARY DUCT LIGATION

The mechanism whereby somatostatin (SS) produces beneficial effects in established pancreatitis induced by pancreaticobiliary duct ligation (PBDL) is still not clear. The aim of the work was to evaluate the pos sibility of a direct action of SS on pancreatic acinar cells from rats with acute pancreatitis. For this purpose, we studied the SS-receptor -adenylate cyclase system in pancreatic acinar membranes from both, co ntrol rats and rats with experimentally induced acute pancreatitis. On the other hand, it has been reported that cholecystokinin (CCK) dimin ishes the number of SS receptors in pancreatic acinar cells. Proglumid e, a CCK receptor antagonist reduces the severity of acute pancreatiti s in the rat. Therefore, we have also examined the effect of proglumid e on the somatostatinergic system in controls and rats with acute panc reatitis. Fourteen hours after PBDL, the SS receptors, the capacity of the SS analogue SMS 201-995 to inhibit forskolin-stimulated adenylate cyclase activity and PTX-catalyzed [P-32] ADP-ribosylation of the alp ha(1) subunits of Gi proteins could not be detected in pancreatic acin ar membranes. One month after reopening the closed pancreaticobiliary duct (PBD), the pancreas showed regeneration of acinar cells, and the above-mentioned parameters were significantly lower than in the contro l group. Two months after reopening the closed PBD, all these paramete rs had returned to control values. The administration of proglumide (2 0 mg/kg i.p.), a cholecystokinin receptor antagonist, accelerated panc reatic regeneration and approached all these parameters to control val ues one month after reopening the closed PBD. The present study sugges ts that the beneficial effects of SS on established pancreatitis induc ed by PBDL may not be due to a direct action of the peptide on pancrea tic acinar cells at least at 14 hours after PBDL. In addition, these f indings suggest that in established pancreatitis the effect of proglum ide on the SS receptor-adenylate cyclase system could be due to its ac tion on pancreatic regeneration.