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5‐HT 2B receptors play a key role in mediating the excitatory effects of 5‐HT in human colon in vitro
Author(s) -
Borman R A,
Tilford N S,
Harmer D W,
Day N,
Ellis E S,
Sheldrick R L G,
Carey J,
Coleman R A,
Baxter G S
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704571
Subject(s) - receptor , myenteric plexus , interstitial cell of cajal , 5 ht receptor , serotonin , excitatory postsynaptic potential , medicine , endocrinology , human gastrointestinal tract , biology , stimulation , gastrointestinal tract , immunohistochemistry , smooth muscle
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‐HT 2B receptors in human colon, and to establish their possible role in the aetiology of IBS. The distribution of 5‐HT 2B receptor mRNA and protein were investigated by quantitative RT – PCR, Western analysis and immunocytochemistry. High levels of both mRNA and protein for 5‐HT 2B receptors were found throughout the human gastrointestinal tract, and in particular in colon, where 5‐HT 2B 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. 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‐HT 2B receptor antagonists. 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‐HT 2B receptors. It is proposed that these receptors contribute to the putative 5‐HT‐induced colonic smooth muscle hypersensitivity associated with IBS.British Journal of Pharmacology (2002) 135 , 1144–1151; doi: 10.1038/sj.bjp.0704571