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

Authors
Oh, Kyung HoonNam, YoonjinJeong, Ji HoonKim, In KyeomSohn, Uy Dong
Issue Date
Apr-2014
Publisher
MDPI AG
Keywords
5-hydroxytryptamine; feline esophageal smooth muscle; DA-9701; Pharbitidis Semen; Corydalis Tuber; MLC20; phosphorylation
Citation
MOLECULES, v.19, no.4, pp 5135 - 5149
Pages
15
Journal Title
MOLECULES
Volume
19
Number
4
Start Page
5135
End Page
5149
URI
https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/12369
DOI
10.3390/molecules19045135
ISSN
1420-3049
1420-3049
Abstract
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(alpha q), G(alpha o) and G(alpha s). 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.
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