Activation of submucosal 5-HT3 receptors elicits a somatostatin-dependent inhibition of ion secretion in rat colon |
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| Authors: | N Yang SM Liu LF Zheng T Ji Y Li XL Mi H Xue W Ren JD Xu XH Zhang LS Li Y Zhang JX Zhu |
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| Affiliation: | 1.Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China;2.Department of Biology, College of Science and Health, University of Wisconsin-La Crosse, La Crosse, WI, USA;3.Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University, Columbus, OH, USA |
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| Abstract: | Background and purpose:5-Hydroxytryptamine (5-HT) is a key regulator of the gastrointestinal system and we have shown that submucosal neuronal 5-HT3 receptors exerted a novel inhibitory effect on colonic ion transport. The aim of the present study was to investigate the precise mechanism(s) underlying this inhibitory effect.Experimental approach:Mucosa/submucosa or mucosa-only preparations from rat distal colon were mounted in Ussing chambers for measurement of short-circuit current (Isc) as an indicator of ion secretion. Somatostatin release was determined with radioimmunoassay. Intracellular cAMP content was measured with enzyme-linked immunoadsorbent assay (elisa). Immunohistochemical techniques were used to study the expression of 5-HT3 receptors, somatostatin and somatostatin receptors in colonic tissue.Key results:In rat distal colonic mucosa/submucosa preparations, pretreatment with 5-HT3 receptor antagonists enhanced 5-HT-induced increases in Isc. However, in mucosa-only preparations without retained neural elements, pretreatment with 5-HT3 receptor antagonists inhibited 5-HT-induced ΔIsc. Pretreatment with a somatostatin-2 (sst2) receptor antagonist in mucosa/submucosa preparations augmented 5-HT-induced ΔIsc. Combination of sst2 and 5-HT3 receptor antagonists did not cause further enhancement of 5-HT-induced ΔIsc. Moreover, both sst2 and 5-HT3 receptor antagonists enhanced 5-HT-induced increase in intracellular cAMP concentration in the mucosa/submucosa preparations. 5-HT released somatostatin from rat colonic mucosa/submucosa preparations, an effect prevented by pretreatment with 5-HT3 receptor antagonists. Immunohistochemical staining demonstrated the presence of 5-HT3 receptors on submucosal somatostatin neurons and of sst2 receptors on colonic mucosa.Conclusion and implications:Activation of neuronal 5-HT3 receptors in the submucosal plexus of rat colon suppressed 5-HT-induced ion secretion by releasing somatostatin from submucosal neurons. |
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| Keywords: | 5-HT3 receptor somatostatin colonic ion transport |
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