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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bruce, Iain C. Jin, Jian Ma, Xin Ru, Xiaochen Cai, Yanfei Xia, Qiang Chen, Yun Yao, Xiaoqiang He, Dongxu |
| Description | Author Affiliation: Ma X ( Department of Cellular and Molecular Pharmacology, Jiangnan University, Wuxi, China. maxin@jiangnan.edu.cn) |
| Abstract | BACKGROUND AND PURPOSE: Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+) -permeable channel with multiple modes of activation. Apigenin is a plant-derived flavone, which has potential preventive effects on the development of cardiovascular disease. We set out to explore the effects of apigenin on TRPV4 channel activity and its role in vasodilatation. EXPERIMENTAL APPROACH: The effects of apigenin (0.01-30 µM) on TPRV4 channels were investigated in HEK293 cells over-expressing TRPV4, rat primary cultured mesenteric artery endothelial cells (MAECs) and isolated small mesenteric arterial segments using whole-cell patch clamp, fluorescent Ca(2+) imaging, intracellular recording and pressure myography. KEY RESULTS: Whole-cell patch clamp and fluorescent Ca(2+) imaging in HEK cells over-expressing TRPV4 showed that apigenin concentration-dependently stimulated the TRPV4-mediated cation current and Ca(2+) influx. In MAECs, apigenin stimulated Ca(2+) influx in a concentration-dependent manner. These increases in cation current and Ca(2+) influx were markedly inhibited by TRPV4-specific blockers and siRNAs. Furthermore, pressure myography and intracellular recording in small third-order mesenteric arteries showed that apigenin dose-dependently evoked smooth muscle cell membrane hyperpolarization and subsequent vascular dilatation, which were significantly inhibited by TRPV4-specific blockers. TRPV4 blocker or charybdotoxin (200 nM) plus apamin (100 nM) diminished the apigenin-induced dilatation. CONCLUSION AND IMPLICATIONS: This is the first study to demonstrate the selective stimulation of TRPV4 by apigenin. Apigenin was found to activate TRPV4 channels in a dose-dependent manner in HEK cells over-expressing TRPV4 and in native endothelial cells. In rat small mesenteric arteries, apigenin acts on TRPV4 in endothelial cells to induce EDHF-mediated vascular dilatation. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 166 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2012-05-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Apigenin Pharmacology Endothelial Cells Drug Effects TRPV Cation Channels Vasodilation Animals Administration & Dosage Calcium Metabolism Dose-Response Relationship, Drug HEK293 Cells Mesenteric Arteries Muscle, Smooth, Vascular Patch-Clamp Techniques Rats, Sprague-Dawley Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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