학술논문
Gastroprokinetic agent, mosapride inhibits 5-HT3 receptor currents in NCB-20 cells
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- 영문명
- 발행기관
- 대한생리학회-대한약리학회
- 저자명
- Yong Soo Park Ki-Wug Sung
- 간행물 정보
- 『The Korean Journal of Physiology & Pharmacology』제23권 제5호, 419~426쪽, 전체 8쪽
- 주제분류
- 의약학 > 의학일반
- 파일형태
- 발행일자
- 2019.09.30
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국문 초록
영문 초록
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.
목차
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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