The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells
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...
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MDPI AG
2014-04-01
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| Series: | Molecules |
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| author | Kyung Hoon Oh Yoonjin Nam Ji Hoon Jeong In Kyeom Kim Uy Dong Sohn |
| author_facet | Kyung Hoon Oh Yoonjin Nam Ji Hoon Jeong In Kyeom Kim Uy Dong Sohn |
| author_sort | Kyung Hoon Oh |
| collection | DOAJ |
| description | 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. |
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| last_indexed | 2024-12-21T07:15:17Z |
| publishDate | 2014-04-01 |
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| spelling | doaj.art-613ca9f460cc4cdf9c27e725a1c50ec52022-12-21T19:11:53ZengMDPI AGMolecules1420-30492014-04-011945135514910.3390/molecules19045135molecules19045135The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle CellsKyung Hoon Oh0Yoonjin Nam1Ji Hoon Jeong2In Kyeom Kim3Uy Dong Sohn4Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, KoreaDepartment of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, KoreaDepartment of Pharmacology, School of Medicine, Chung-Ang University, Seoul 156-756, KoreaDepartment of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, KoreaDepartment of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, KoreaSerotonin, 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.http://www.mdpi.com/1420-3049/19/4/51355-hydroxytryptaminefeline esophageal smooth muscleDA-9701Pharbitidis SemenCorydalis TuberMLC20phosphorylation |
| spellingShingle | Kyung Hoon Oh Yoonjin Nam Ji Hoon Jeong In Kyeom Kim Uy Dong Sohn The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells Molecules 5-hydroxytryptamine feline esophageal smooth muscle DA-9701 Pharbitidis Semen Corydalis Tuber MLC20 phosphorylation |
| title | The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells |
| title_full | The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells |
| title_fullStr | The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells |
| title_full_unstemmed | The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells |
| title_short | The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells |
| title_sort | effect of da 9701 on 5 hydroxytryptamine induced contraction of feline esophageal smooth muscle cells |
| topic | 5-hydroxytryptamine feline esophageal smooth muscle DA-9701 Pharbitidis Semen Corydalis Tuber MLC20 phosphorylation |
| url | http://www.mdpi.com/1420-3049/19/4/5135 |
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