Bombesin induces a reduction of somatostatin inhibition of adenylyl cyclase activity, Gi function, and somatostatin receptors in rat exocrine pancreas
Authors
Álvaro Alonso, Itziar; Muñoz Acedo, Gema; Rodríguez Martín, EulaliaIdentifiers
Permanent link (URI): http://hdl.handle.net/10017/2361DOI: 10.1016/S0196-9781(99)00054-6
ISSN: 0196-9781
Publisher
Elsevier
Date
1999Bibliographic citation
Peptides, 1999, v. 20, n. 6, p. 723–730
Keywords
Bombesin
RC-3095
Proglumide
Somatostatin receptor
G-protein
Adenylyl cyclase
Project
PM95–0041 (Ministerio de Educación y Cultura)
001/96 (Universidad de Alcalá)
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Publisher's version
http://dx.doi.org/10.1016/S0196-9781(99)00054-6Rights
© Elsevier Science Inc., 1999
Access rights
info:eu-repo/semantics/openAccess
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 ¿g/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,Leu13¿(CH2NH)Leu14]bombesin (6-14) (RC-3095) (10 ¿g/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.
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