Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China. qdfyhbg@16Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, China.Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China.Department of Pathophysiology, Medical College, Qingdao University, Qingdao, China.Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, China.Department of Physiology, Taishan Medical University, Taian, China.AffiliationsCenter for Medical Research, The Affiliated Hospital of Qingdao University, Qingdao, China.com.
Background: Whether 7,8-dihydroxyflavone , a tyrosine kinase receptor B agonist, modulates colonic smooth muscle motility and/or alleviates constipation has not yet been studied. Aims: Here, we aimed to determine how 7,8-DHF influences carbachol -stimulated contraction of colonic strips and the in vivo effect of 7,8-DHF on constipation. Methods: Muscle strips were isolated from rat colons for recording contractile tension and performing western blotting. Constipation was induced in rats with lo...更多
Background: Whether 7,8-dihydroxyflavone , a tyrosine kinase receptor B agonist, modulates colonic smooth muscle motility and/or alleviates constipation has not yet been studied. Aims: Here, we aimed to determine how 7,8-DHF influences carbachol -stimulated contraction of colonic strips and the in vivo effect of 7,8-DHF on constipation. Methods: Muscle strips were isolated from rat colons for recording contractile tension and performing western blotting. Constipation was induced in rats with loperamide. Results: Although it specifically activated TrkB, 7,8-DHF applied alone neither activated PLCγ1 in the colonic strips nor induced colonic strip contraction. However, 7,8-DHF enhanced CCh-stimulated PLCγ1 activation and strip contraction. The PLCγ1 antagonist U73122 suppressed both CCh-stimulated and 7,8-DHF-enhanced/CCh-stimulated contraction. While clarifying the underlying mechanism, we revealed that 7,8-DHF augmented muscarinic M3 receptor expression in the colonic strips. The M3-selective antagonist tarafenacin specifically inhibited the 7,8-DHF-enhanced/CCh-stimulated contraction of the colonic strips. Since 7,8-DHF increased Akt phosphorylation, and LY294002 dramatically inhibited both 7,8-DHF-augmented M3 expression and 7,8-DHF-enhanced/CCh-stimulated contractions, we assumed that 7,8-DHF/TrkB/Akt was associated with the modulation of M3 expression in the colonic strips. ANA-12, a specific TrkB antagonist, not only inhibited TrkB activation by 7,8-DHF but also suppressed 7,8-DHF-enhanced cholinergic contraction, 7,8-DHF/CCh-mediated activation of PLCγ1/Akt, and M3 overexpression in colonic strips. In vivo 7,8-DHF, also by promoting intestinal motility and M3 expression, significantly alleviated loperamide-induced functional constipation in rats. Conclusions: Our results suggest that 7,8-DHF regulates colonic motility possibly via a TrkB/Akt/M3 pathway and may be applicable for alleviating constipation.收起
