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

I. Álvaro-Alonso, G. Muñoz-Acedo, E. Rodríguez-Martín, A. V. Schally, E. Arilla

Research output: Contribution to journalArticle

4 Scopus citations

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 μg/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,Leu13ψ(CH2NH)Leu14]bombesin (6-14) (RC-3095) (10 μg/kg ip), 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. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)723-730
Number of pages8
JournalPeptides
Volume20
Issue number6
DOIs
StatePublished - Aug 1 1999
Externally publishedYes

Keywords

  • Adenylyl cyclase
  • Bombesin
  • G(i) protein
  • Proglumide
  • RC-3095
  • Somatostatin receptor

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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