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 possibility 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, control rats and rats with experimentally induced
acute pancreatitis. On the other hand, it has been reported that
cholecystokinin (CCK) diminishes the number of SS receptors in pancreatic acinar cells.
Proglumide, a
CCK receptor antagonist reduces the severity of
acute pancreatitis in the rat. Therefore, we have also examined the effect of
proglumide on the somatostatinergic system in controls and rats with
acute pancreatitis. 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 [32P] ADP-ribosylation of the alpha1 subunits of Gi
proteins could not be detected in pancreatic acinar 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 control group. Two months after reopening the closed PBD, all these parameters had returned to control values. The administration of
proglumide (20 mg/kg i.p.), a
cholecystokinin receptor antagonist, accelerated pancreatic regeneration and approached all these parameters to control values one month after reopening the closed PBD. The present study suggests that the beneficial effects of SS on established
pancreatitis induced by PBDL may not be due to a direct action of the
peptide on pancreatic acinar cells at least at 14 hours after PBDL. In addition, these findings suggest that in established
pancreatitis the effect of
proglumide on the SS receptor-
adenylate cyclase system could be due to its action on pancreatic regeneration.