Somatostatin Receptor type 2 Mediates Bombesin‐Induced Inhibition of Gastric Acid Secretion in Mice

Journal of Physiology - Tập 549 Số 3 - Trang 889-901 - 2003
Laura Piqueras1, Yvette Taché2, Vicente Martı́nez1
1Department of Physiology, Pharmacology and Toxicology, Cardenal Herrera CEU University, Valencia, Spain
2CURE: Digestive Diseases Research Center, VA Greater Los Angeles Health Care System, Department of Medicine and Brain Research Institute, University of California-Los Angeles, Los Angeles, CA, USA

Tóm tắt

Studies in isolated mouse stomach showed that bombesin releases somatostatin. We characterized the effects of exogenous bombesin on gastric acid secretion in mice and determined the involvement of somatostatin and somatostatin receptor type 2 (SSTR2) by using somatostatin immunoneutralization, the SSTR2 antagonist, PRL‐2903, and SSTR2 knockout mice. Gastric acid secretion was monitored under basal and pentagastrin‐, histamine‐ or bethanechol‐stimulated conditions in urethane‐anaesthetized mice. Bombesin (10–40 μg kg−1 h−1) and somatostatin‐14 (20 μg kg−1 h−1) were infused i.v. 10 and 30 min after PRL‐2903 or somatostatin antibody pretreatment, respectively. Urethane‐anaesthetized wild‐type mice had low basal acid secretion (0.12 ± 0.01 μmol (10 min)−1) compared with SSTR2 knockout mice (1.43 ± 0.10 μmol (10 min)−1). Somatostatin antibody and PRL‐2903 increased basal secretion in wild‐type mice but not in SSTR2 knockout animals. In wild‐type mice, bombesin inhibited secretagogue‐stimulated acid secretion in a dose‐dependent manner, and somatostatin‐14 inhibited pentagastrin‐stimulated secretion. In wild‐type mice pretreated with somatostatin antibody or PRL‐2903 and in SSTR2 knockout mice, bombesin and somatostatin‐14 i.v. infusion did not alter the increased gastric acid secretion. These results indicate that, in mice, bombesin inhibits gastric acid secretion through the release of somatostatin and the activation of SSTR2. These observations strengthen the important role of SSTR2 in mediating somatostatin inhibitory actions on gastric acid secretion.

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Journal of Physiology

Tập 549 Số 3

889-901

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