Drug Design, Development and Therapy (Feb 2021)
Effect of Evodiamine on Rat Colonic Hypermotility Induced by Water Avoidance Stress and the Underlying Mechanism
Abstract
HaiXia Ren,1,* FangTing Yuan,1,2,* Wei Tan,1 YiJuan Ding,1 Ping An,1 HeSheng Luo1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 2Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: HeSheng Luo Email [email protected] and Aim: EVO is a natural alkaloid that reportedly has potential value in regulating gastrointestinal motility, but this conclusion remains controversial, and the molecular mechanism is unclear. In this study, we aimed to explore the effect of short-chain fatty acids on rat colonic hypermotility induced by water avoidance stress and the underlying mechanism.Methods: We constructed a hypermotile rat model by chronic water avoidance stress, and Western blot was used to detect the protein level of nNOS in colon tissue. The organ bath and multichannel physiological signal acquisition systems were used to examine the spontaneous contractions of smooth muscle strips. The whole‐cell patch‐clamp technique was used to investigate L‐type voltage‐dependent calcium and BKCa channel currents in colonic smooth muscle cells.Results: EVO inhibited the spontaneous contractions of colonic smooth muscle strips in a dose-dependent manner. Moreover, EVO decreased the fecal output induced by chronic water avoidance stress. TTX did not block the inhibitory effect of EVO on spontaneous colon contractions, while L-NNA, a selective nNOS synthase inhibitor, did partially abolish this inhibitory effect. The protein expression of nNOS in the colon tissues of rats administered EVO was significantly increased compared to that in control rats. EVO reversibly inhibited the L-type calcium channel current without changing the steady-state activation or inactivation in colonic smooth muscle cells. EVO significantly inhibited the BKCa current but did not change the shape of the I‐V curves.Conclusion: EVO inhibits gastrointestinal motility by inhibiting L-type calcium and BKCa channels in colonic smooth muscle cells and indirectly interacting with nNOS.Keywords: evodiamine, gastrointestinal motility, nitric oxide, L‐type voltage‐dependent calcium channels, BKCa channel
