# Looking at new 5ht receptors



## eric (Jul 8, 1999)

FYIBr 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. PMID: 11877320 [PubMed - in process] Still haven't found the receptor yet, but at least there studying all of them.Interestinng this receptor seems to be the "excitatory effects" one it would seem and that may have some good clinical value down the road for sure.


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## wanderingstar (Dec 1, 1999)

Thanks for posting eric.







I just wish some sort of pharmecutical or otherwise intervention could be developed pronto - I always feel this frustration whenever I read research. It's like with ME/CFS - the research is never turned into effective treatment.


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## Mike NoLomotil (Jun 6, 2000)

ORBITING LIGHT SOURCE:One of the more promising aspects of studying ANY excitatory receptor sites which are "colonic" is for better pharmacotherapy for c-types, the more stubborn and inscrutable symptom set. Irrespective of mechanism, there are so many intracellular sources of 5HT in the gut immunocytes (fixed and circulating) that understanding the d-prone etiology is comparatively simple since it is easy to show where the observable upregulation of motor and sensory nerves can come from and what can elicit it (ie: anything which provokes certain immunocytes to degaranulate or apoptosize) provides an immediate and abundant local source of this transmitter directly to the effector site. Often mediators like PAF are released which will recruit more serotonin release from platelets...of which there are vast numbers in the microcirculation of the gut at any time). It is also easy to observe the effects of EC cells and nitric oxide and a host of other motility-enhancing sources which are involved at various times in the "d-process".The c-type patients who truly have been diagnosed correctly face relatively tougher road as they have less options and respond less to prophylactic therapies as the prophylactic therapies available have far less effect since the neuromuscular, endocrine, and immunologic mechanics differ. In simple terms, while there do exist pharamcotherapies, often the drugs effect on motility is minimal where you want it and more pronounced where you do not want it. If, for example 5HT(2B) receptors are excitatory with some specificty in the lower colon, then delivery of a locally effective stimulus which can enhance evacuation on command with minimal untoward effects would surely be welcome!This to me, looking at the big picture, is the far greater challenge among the subpopulations especially since the effectd population is smaller (thus representing a smaller market for any end product). But while the drugs developed so far for this symptom set are each at best a compromise, I do no think that a better solution is far away.And at least there are more OTC aids available now then there ever have been in this market and the number I think is slowly growing as more Eurocentric and Asiocentric therapies are brought to the US market.Eat well. Think well. be well.MNL


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