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 (pD2 = 5.19). This response was subject to desensitization and was mimicked by the indolealkylamines with a rank order potency of 5-HT approximately alpha-methyl-5-HT > 5-carboxytryptamine approximately 5-methoxytryptamine. 2-Methyl-5-HT was a partial agonist. The colonic response to 5-HT was unaltered by methysergide (10 microM), ritanserin (0.1 microM), ondansetron (1 microM) or clozapine (10 microM), but was antagonized by the 5-HT4 receptor antagonists SB204070 (pD'2 = 9.32), GR113808 (pKb = 8.56), DAU6285 (pKb = 6.07) and SDZ205557 (pKb = 6.80). The response of colonic epithelial and oesophageal tunica 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.
Goldhill
J
J
Department of Internal Medicine, Synthélabo Recherche, Rueil Malmaison, France.
Porquet
M F
MF
Angel
I
I
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D007103:Immobilization; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D008297:Male; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin