The response of rat colonic mucosa to 5-hydroxytryptamine in health and following restraint stress

The present study characterized the rat colonic secretory response to 5-hydroxytryptamine (5-HT) and determined alterations in this response following stress. 5-HT stimulated rat colonic short-circuit current in a concentration-dependent fashion (pD(2) = 5.19). This response was subject to desensitization and was mimicked by the indolealkylamines with a rank order potency of 5-HT approximate to alpha-methyl-5-HT > 5-carboxytryptamine approximate to 5-methoxytryptamine. 2-Methyl-5-HT was a partial agonist. The colonic response to 5-HT was unaltered by methysergide (10 mu M), ritanserin (0.1 mu M), ondansetron (1 mu M) or clozapine (10 mu M), but was antagonized by the 5-HT4 receptor antagonists SB204070 (pD'(2) = 9.32), GR113808 (pK(b) = 8.56), DAU6285 (pK(b) = 6.07) and SDZ205557 (pK(b) = 6.80). The response of colonic epithelial and oesophageal tunics muscularis mucosae to 5-HT is therefore mediated by a similar 5-HT4 receptor. Following wrap restraint stress, the colonic response to 5-HT became bimodal. Half of the preparations were hyper-responsive, while the rest were hypo-responsive to 5-HT. This 5-HT4 receptor may therefore be involved in stress related changes in fluid transport. (C) 1998 Elsevier Science B.V. All rights reserved.