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《中国生理学会第24届全国会员代表大会暨生理学学术大会论文汇编》2014年
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Hyperpolarisation Activated cAMP-Gated Cation Channels Drive Serotonin Release And Sensory Activity From The Gut

Yingping Wang  Biying Sun  Ping Luo  Li Dong  Qian Li  Guohua Zhang  戎伟芳  
【摘要】:The hyperpolarisation activated c AMP-gated cation channels(HCNs)belong to the cyclic nucleotide-gated(CNG)channel family and consist of four subtypes,HCN1-4.These channels are known to be expressed in the heart where they play important roles in the generation of the cardiac rhythm.Subtypes of HCNs are also expressed in non-cardiac tissues.We have previously shown that HCN2 and HCN3 were differentially expressed in spinal and vagal primary afferent neurons of the small intestine.HCN blockers attenuated the vagal component of the mesenteric afferent response to distension of the normal gut.Hence,HCNs appeared to play a role in priming the vagal but not spinal afferents in the normal condition.In this work we further investigated the possible expression and function of HCNs within the gut.Immunofluorescent staining showed HCNs being distinctively expressed in the enterochromaffin(EC)cells of the mice,the rat and the human gut.We then investigated the possible role of HCNs in regulation of 5-HT release through real-time amperometric measurement in an isolated murine gut preparation.Cyclic AMP was shown to increase 5-HT release and the mesenteric afferent nerve activity.The effect was reversible by HCN blockers,ZD7288 and Cs Cl,which could also inhibit the basal 5-HT release.5-HT3 receptor antagonist,tropisetron,also blocked the afferent nerve response to c AMP.Since cholera toxin(CT)is known to increase c AMP level and 5-HT release,we tested whether activation of HCNs might underlie CT-induced 5-HT release and afferent nerve activity.As expected,CT caused a slowly developing increase in 5-HT release and afferent nerve activity,which were reversed by ZD7288.Again,tropisetron was able to inhibit CT-induced afferent discharge.These results suggest that HCNs drive serotonin release and afferent nerve activity in the gut.We propose HCNs might represent a novel therapeutic target for inflammatory or functional bowl diseases.

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