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Distribution of 5-HT_{3}, 5-HT_{4}, and 5-HT_{7} Receptors Along the Human Colon
( Nor S Yaakob ),( Kenneth A Chinkwo ),( Navinisha Chetty ),( Ian M Coupar ),( Helen R Irving ) 대한소화기기능성질환·운동학회 2015 Journal of Neurogastroenterology and Motility (JNM Vol.21 No.3
Background/Aims: Several disorders of the gastrointestinal tract are associated with abnormal serotonin (5-HT) signaling or metabolism where the 5-HT_{3} and 5-HT_{4} receptors are clinically relevant. The aim was to examine the distribution of 5-HT_{3}, 5-HT_{4}, and 5-HT_{7} receptors in the normal human colon and how this is associated with receptor interacting chaperone 3, G protein coupled receptor kinases, and protein LIN-7 homologs to extend previous observations limited to the sigmoid colon or the upper intestine. Methods: Samples from ascending, transverse, descending, and sigmoid human colon were dissected into 3 separate layers (mucosa, longitudinal, and circular muscles) and ileum samples were dissected into mucosa and muscle layers (n = 20). Complementary DNA was synthesized by reverse transcription from extracted RNA and expression was determined by quantitative or end point polymerase chain reaction. Results: The 5-HT_{3} receptor subunits were found in all tissues throughout the colon and ileum. The A subunit was detected in all samples and the C subunit was expressed at similar levels while the B subunit was expressed at lower levels and less frequently. The 5-HT_{3} receptor E subunit was mainly found in the mucosa layers. All splice variants of the 5-HT_{4} and 5-HT_{7} receptors were expressed throughout the colon although the 5-HT_{4} receptor d, g, and i variants were expressed less often. Conclusions: The major differences in 5-HT receptor distribution within the human colon are in relation to the mucosa and muscular tissue layers where the 5-HT_{3} receptor E subunit is predominantly found in the mucosal layer which may be of therapeutic relevance. (J Neurogastroenterol Motil 2015;21:361-369)