Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 135, Issue 5, Pages 1144-1151Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjp.0704571
Keywords
5-hydroxytryptamine; 5-HT2B; human colon; irritable bowel syndrome; motility disorders
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1 5-Hydroxytryptamine (5-HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be established. The aim of the present study was to investigate the distribution and function of 5-HT2B receptors in human colon, and to establish their possible role in the aetiology of IBS. 2 The distribution of 5-HT2B receptor mRNA and protein were, investigated by quantitative RTPCR, Western analysis and immunocytochemistry. High levels of both mRNA and protein for 5HT(2B) receptors were found throughout the human gastrointestinal tract, and in particular in colon, where 5-HT2B receptors were found predominantly in the longitudinal and circular smooth muscle layers within the muscularis externa. and in the myenteric nerve plexus lying between these two layers. 3 Electrical field stimulation of longitudinal muscle preparations of human colon mounted in organ baths resulted in neuronally-mediated contractile responses, that were significantly potentiated by application of 5-HT (up to 10(-7) m), with a pEC(50) of 8.2 +/- 0.1 (n = 49 donors). The response to 5-HT was inhibited by a number of selective 5-HT2B receptor antagonists. 4 This study has shown for the first time that, in contrast to animal studies. the excitatory effects of 5-HT in human colon are mediated by 5-HT2B receptors. It is proposed that these receptors contribute to the putative 5-HT-induced colonic smooth muscle hypersensitivity associated with IBS.
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