Bombesin induces a reduction of somatostatin inhibition of adenylyl cyclase activity, G(i) function, and somatostatin receptors in rat exocrine pancreas

To analyze the effect of bombesin on the somatostatin (SS) mechanism of act ion in the exocrine pancreas, male Wistar rats (250-270 g) were injected in traperitoneally with bombesin (10 mu g/kg) three times daily at 8-h interva ls for 7 or 14 days, Bombesin attenuated the ability of SS to inhibit forsk olin-stimulated adenylyl cyclase activity in pancreatic acinar membranes. H owever, it did not decrease the ability of forskolin to stimulate the adeny lyl cyclase catalytic subunit. The ability of 5'-guanylylimidodiphosphate [ Gpp(NH)p] (a nonhydrolyzable GTP analog) to inhibit forskolin-stimulated ad enylyl cyclase activity was diminished in pancreatic acinar cell membranes from bombesin-treated rats, Bombesin administration did not affect the ADP- ribosylation of a 41-kDa G protein catalyzed by pertussis toxin. The maxima l SS binding capacity of pancreatic acinar membranes from bombesin-treated rats was decreased when compared with controls at the two time periods stud ied. The bombesin/gastrin-releasing peptide antagonist [D-Tpi(6),Leu(13)psi (CH2NH)Leu(14)]bombesin (6-14) (RC-3095) (10 mu g/kg ip), injected three ti mes daily at 8-h intervals for 7 or 14 days, had a similar effect to that o f bombesin on the SS mechanism of action. The combined administration of bo mbesin and its antagonist RC-3095 had a greater effect on the SS receptor-e ffector system than when administered separately. The present study indicat es that the pancreatic SS receptor-effector system may be regulated by bomb esin in vivo. (C) 1999 Elsevier Science Inc. All rights reserved.