title: Bombesin induces a reduction of somatostatin inhibition of adenylyl cyclase activity, Gi function, and somatostatin receptors in rat exocrine pancreas.
abstract: To analyze the effect of bombesin on the somatostatin (SS) mechanism of action in the exocrine pancreas, male Wistar rats (250-270 g) were injected intraperitoneally with bombesin (10 microg/kg) three times daily at 8-h intervals for 7 or 14 days. Bombesin attenuated the ability of SS to inhibit forskolin-stimulated adenylyl cyclase activity in pancreatic acinar membranes. However, it did not decrease the ability of forskolin to stimulate the adenylyl cyclase catalytic subunit. The ability of 5'-guanylylimidodiphosphate [Gpp(NH)p] (a nonhydrolyzable GTP analog) to inhibit forskolin-stimulated adenylyl 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 maximal SS binding capacity of pancreatic acinar membranes from bombesin-treated rats was decreased when compared with controls at the two time periods studied. The bombesin/gastrin-releasing peptide antagonist [D-Tpi6,Leu13psi(CH2NH)Leu14]bombesin (6-14) (RC-3095) (10 microg/kg i.p.), injected three times daily at 8-h intervals for 7 or 14 days, had a similar effect to that of bombesin on the SS mechanism of action. The combined administration of bombesin and its antagonist RC-3095 had a greater effect on the SS receptor-effector system than when administered separately. The present study indicates that the pancreatic SS receptor-effector system may be regulated by bombesin in vivo.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Alvaro-Alonso
authors.forename: G
authors.initials: G
authors.lastname: Muñoz-Acedo
authors.forename: E
authors.initials: E
authors.lastname: Rodríguez-Martín
authors.forename: A V
authors.initials: AV
authors.lastname: Schally
authors.forename: E
authors.initials: E
authors.lastname: Arilla
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors; D017481:Receptors, Somatostatin / Q000187:drug effects*; D013004:Somatostatin / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D010446:Peptide Fragments; D018004:Receptors, Bombesin; D017481:Receptors, Somatostatin; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D013004:Somatostatin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D001839:Bombesin