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Molecules 2014, 19(4), 5135-5149; doi:10.3390/molecules19045135
Article

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

1
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1
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2
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3
 and
1,*
1 Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea 2 Department of Pharmacology, School of Medicine, Chung-Ang University, Seoul 156-756, Korea 3 Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Korea
* Author to whom correspondence should be addressed.
Received: 7 February 2014 / Revised: 8 April 2014 / Accepted: 15 April 2014 / Published: 22 April 2014
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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 Gαq, Gαo and Gαs. 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.
Keywords: 5-hydroxytryptamine; feline esophageal smooth muscle; DA-9701; Pharbitidis Semen; Corydalis Tuber; MLC20; phosphorylation 5-hydroxytryptamine; feline esophageal smooth muscle; DA-9701; Pharbitidis Semen; Corydalis Tuber; MLC20; phosphorylation
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Oh, K.H.; Nam, Y.; Jeong, J.H.; Kim, I.K.; Sohn, U.D. The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells. Molecules 2014, 19, 5135-5149.

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