Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome

摘要

＜正＞ Background The 5-hydroxytryptamine7 receptor （5-HT7 receptor,5-HT7R） plays an important role in the regulation ofsmooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinaldyskinesia,abdominal pain and visceral paresthesia in irritable bowel syndrome （IBS）.The aim of this study was toinvestigate the role of the 5-HT7 receptor in the pathogenesis of IBS.Methods A rat model of irritable bowel syndrome with diarrhea （IBS-D） was established by colonic instillation of aceticacid and restraint stress.A rat model with irritable bowel syndrome with constipation （IBS-C） was established by stomachirrigated with 0-4℃ cool water daily for 14 days.The content and distribution of 5-HT in the brain and gut were examinedby immunohistochemistry and the mRNA expression of the 5-HT7 receptor was determined by fluorescent quantitativereverse transcription polymerase chain reaction.The accumulation of cyclic adenosine monophosphate （cAMP） in all thesame tissues was measured by radioimmunity.Results The models of IBS were reliable by identification.The immunohistochemistry results showed that there weresignificantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus,hypothalamus,jejunum,ileum,proximate colon and distal colon （P＜0.05）,as well as more than were found in the IBS-C group in jejunumand ileum （P＜0.05）.There were more 5-HT positive cells in the IBS-C group than in the control hippocampus,hypothalamus,ileum,proximate colon,and distal colon （P＜0.05）.Real time-PCR results showed that the expressionlevel of the 5-HT7 receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in thehippocampus and hypothalamus （P＜0.05）.The expression level of 5-HT7 receptors in the IBS-C group was notablygreater when compared with the controls in the ileum and colon （P＜0.05）.The cAMP accumulation in the hippocampusand hypothalamus in both the IBS-C and IBS-D groups was higher than that in the control group （P＜0.01 and P＜0.05）.The cAMP accumulation in the IBS-C group was higher than that in the control group in the proximal and distal colon（m＜0.05）.Conclusions The increased 5-HT content in the brain and intestine is related to the IBS pathogenesis.Theup-regulated expression of the 5-HT7 receptor in the brain and colon might play an important role in the pathogenesis ofIBS-C.