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Discussion Starter · #1 ·
they seem to be starting to look at receptors that influence 5HT -Br J Pharmacol 2002 Mar 5;135(5):1144-51 Related Articles, Books, LinkOut 5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro.Borman RA, Tilford NS, Harmer DW, Day N, Ellis ES, Sheldrick RL, Carey J, Coleman RA, Baxter GS.Pharmagene Laboratories Ltd., Orchard Road, Royston, Hertfordshire, SG8 5HD, U.K. Current address: BioWisdom Ltd., Babraham Institute, Babraham, Cambridge, CB2 4AT, U.K.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 8.2plus minus0.1 (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.tom
 

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more on serotonin receptors:Int J Dev Neurosci 2001 Jul;19(4):365-72 Related Articles, Books, LinkOut Developmentally regulated serotonin 5-HT2B receptors.Nebigil CG, Etienne N, Schaerlinger B, Hickel P, Launay JM, Maroteaux L.Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, Universite L. Pasteur de Strasbourg, BP 163-67404 Cedex, Illkirch, France.Serotonin (5-hydroxytryptamine, 5-HT) binds to numerous cognate receptors to initiate its biological effects. In this review, we have focused on the 5-HT2B receptor to address how signaling and expression of this receptor is specifically implicated in embryonic development and adult health and disease. Transduction of the 5-HT2B signaling is complex, including phospholipase C and A2 stimulation, cGMP production and a mitogenic signal that integrates the tyrosine kinase-signaling pathway. Furthermore, 5-HT, through the 5-HT2B receptors, has the ability to control serotonergic differentiation of committed neuron-like cells. In addition, 5-HT2B receptors are actively involved in the transient action of 5-HT during embryonic morphogenesis. Our recent data presented the first genetic evidence that 5-HT via 5-HT2B receptors regulates cardiac embryonic development and adult functions and suggested that this receptor subtype may be involved in other physiopathological situations. In particular, 5-HT-dependent molecular mechanisms may be involved in embryonic development and postnatal maturation of the enteric nervous system. Also, the involvement of the 5-HT2B receptor in the vascular growth often observed in hypertension is likely. These probably result from reactivation of developmentally regulated receptors in pathological situations. Finally, embryonic functions of 5-HT2 receptors observed in Drosophila gastrulation suggest evolutionary conserved mechanisms.tom
 

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Discussion Starter · #3 ·
more on serotonin receptors:Int J Dev Neurosci 2001 Jul;19(4):365-72 Related Articles, Books, LinkOut Developmentally regulated serotonin 5-HT2B receptors.Nebigil CG, Etienne N, Schaerlinger B, Hickel P, Launay JM, Maroteaux L.Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, Universite L. Pasteur de Strasbourg, BP 163-67404 Cedex, Illkirch, France.Serotonin (5-hydroxytryptamine, 5-HT) binds to numerous cognate receptors to initiate its biological effects. In this review, we have focused on the 5-HT2B receptor to address how signaling and expression of this receptor is specifically implicated in embryonic development and adult health and disease. Transduction of the 5-HT2B signaling is complex, including phospholipase C and A2 stimulation, cGMP production and a mitogenic signal that integrates the tyrosine kinase-signaling pathway. Furthermore, 5-HT, through the 5-HT2B receptors, has the ability to control serotonergic differentiation of committed neuron-like cells. In addition, 5-HT2B receptors are actively involved in the transient action of 5-HT during embryonic morphogenesis. Our recent data presented the first genetic evidence that 5-HT via 5-HT2B receptors regulates cardiac embryonic development and adult functions and suggested that this receptor subtype may be involved in other physiopathological situations. In particular, 5-HT-dependent molecular mechanisms may be involved in embryonic development and postnatal maturation of the enteric nervous system. Also, the involvement of the 5-HT2B receptor in the vascular growth often observed in hypertension is likely. These probably result from reactivation of developmentally regulated receptors in pathological situations. Finally, embryonic functions of 5-HT2 receptors observed in Drosophila gastrulation suggest evolutionary conserved mechanisms.tom
 
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