The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells

Molecules

Kyung Hoon Oh²  Yoonjin Nam²  Ji Hoon Jeong¹  In Kyeom Kim³ 

[1] Department of Pharmacology, School of Medicine, Chung-Ang University, Seoul 156-756, Korea; E-Mail:;Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea; E-Mails:;Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Korea; E-Mail:

关键词: 5-hydroxytryptamine;    feline esophageal smooth muscle;    DA-9701;    Pharbitidis Semen;    Corydalis Tuber;    MLC₂₀;    phosphorylation;   

DOI  :  10.3390/molecules19045135

来源: mdpi

【 摘 要 】

Serotonin, or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter found in blood platelets, the gastrointestinal (GI) tract, and the central nervous system (CNS) of animals and humans. The signaling pathways of 5-hydroxytryptamine (5-HT)-induced contractions in cat esophageal smooth muscle cell (ESMC)s have been identified, but the downstream components of the 5-HT signaling pathway remain unclear. DA-9701 is the standardized extract of the Pharbitis nil Choisy seed (Pharbitidis Semen, Convolvulaceae) and the root of Corydalis yahusuo W.T. Wang (Corydalis Tuber, Papaveraceae). DA-9701 is known to have strong gastroprokinetic effects and a good safety profile. In this study, we investigated the 5-HT signaling pathway at the G-protein level, and we explored the mechanisms by which DA-9701 induces smooth muscle contraction. Freshly isolated smooth muscle cells were harvested from the feline esophagus, and cells were permeabilized to measure their length. 5-HT produced esophageal smooth muscle contractions in a dose-dependent manner. Furthermore, 5-HT produced a relatively long-acting contraction. 5-HT binds to the 5-HT₂, 5-HT₃ and 5-HT₄ receptors to induce smooth muscle contraction in feline ESMCs. These receptors, which are located in esophageal smooth muscle, are coupled to G_αq, G_αo and G_αs. These G proteins activate PLC, which leads to Ca²⁺/calmodulin-dependent MLCK activation, resulting in MLC₂₀ phosphorylation and cell contraction. Conversely, DA-9701 inhibits 5-HT-induced contraction by inhibiting MLC₂₀ phosphorylation.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.