Abstract
Somatostatin, probably acting through somatostatin type 2 receptors (SSTR2), is the main inhibitor of gastric acid secretion. We characterized gastric acid secretion in SSTR2 knockout mice, and used preferential somatostatin receptor agonists to assess the relative role of SSTR1, 2, 3, 4, and 5 on gastric acid secretion. Basal gastric acid secretion and the secretory response to a meal were similar in conscious wild-type and knockout mice. However, under urethane anesthesia, which releases endogenous somatostatin, SSTR2 knockout mice had a basal secretion 11-15-fold higher than wild-type animals (micromol/10 min:1.40+/-0.09 vs. 0.10+/-0.01, p<0.05). Gastrin immunoneutralization or H(2) receptors blockade (cimetidine), but not cholinergic blockade (atropine), reduced the high basal secretion in SSTR2 knockout mice. In SSTR2 knockout mice, gastrin and histamine stimulated acid secretion with similar efficacy, while in wild-type mice histamine was more effective than gastrin. SSTR2 knockout mice showed also a hypersecretory response to pylorus ligation compared with wild-type animals. In wild-type mice, somatostatin-14, SMS 201-995, and the SSTR2-preferential agonist, DC 32-87, inhibited gastrin-stimulated acid secretion with an order of potency SMS 201-995>DC 32-87>somatostatin-14. Preferential agonists for the SSTR1, 3, 4, and 5 were devoid of any effect. None of the compounds tested affected the high basal secretion observed under urethane anesthesia in SSTR2 knockout mice. These results show that gastric antisecretory effects of peripheral somatostatin are mediated solely through SSTR2. In the absence of functional SSTR2 other somatostatin receptors do not compensate for the lack somatostatin-SSTR2-mediated inhibition. Basal acid secretion and the response to a meal are normal in conscious SSTR2 knockout mice, suggesting the presence of somatostatin-independent mechanisms that compensate for the lack of somatostatin-SSTR2-mediated inhibitory responses.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
