Gastroprokinetic agent, mosapride inhibits 5-HT₃ receptor currents in NCB-20 cells
10.4196/kjpp.2019.23.5.419
- Author:
Yong Soo PARK
1
;
Ki Wug SUNG
Author Information
1. Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
- Publication Type:Original Article
- Keywords:
Gastroprokinetic;
Mosapride;
Patch clamp;
5-hydroxytryptamine3 receptor
- MeSH:
Gastric Emptying;
Methods;
Serotonin
- From:The Korean Journal of Physiology and Pharmacology
2019;23(5):419-426
- CountryRepublic of Korea
- Language:English
-
Abstract:
Mosapride accelerates gastric emptying by acting on 5-hydroxytryptamine type 4 (5-HT₄) receptor and is frequently used in the treatment of gastrointestinal (GI) disorders requiring gastroprokinetic efficacy. We tested the effect of mosapride on 5-hydroxytryptamine type 3 (5-HT₃) receptor currents because the 5-HT₃ receptors are also known to be expressed in the GI system and have an important role in the regulation of GI functions. Using the whole-cell voltage clamp method, we compared the currents of the 5-HT₃ receptors when 5-HT was applied alone or was co-applied with mosapride in cultured NCB-20 cells known to express 5-HT₃ receptors. The 5-HT₃ receptor current amplitudes were inhibited by mosapride in a concentration-dependent manner. Mosapride blocked the peak currents evoked by the application of 5-HT in a competitive manner because the EC₅₀ shifted to the right without changing the maximal effect. The rise slopes of 5-HT₃ receptor currents were decreased by mosapride. Pre-application of mosapride before co-application, augmented the inhibitory effect of mosapride, which suggests a closed channel blocking mechanism. Mosapride also blocked the opened 5-HT₃ receptor because it inhibited the 5-HT₃ receptor current in the middle of the application of 5-HT. It accelerated desensitization of the 5-HT₃ receptor but did not change the recovery process from the receptor desensitization. There were no voltage-, or use-dependency in its blocking effects. These results suggest that mosapride inhibited the 5-HT₃ receptor through a competitive blocking mechanism probably by binding to the receptor in closed state, which could be involved in the pharmacological effects of mosapride to treat GI disorders.
