| 14642777 |
Jiang J, Backx PH, Teoh H, Ward ME: Role of Cl- currents in rat aortic smooth muscle activation by prostaglandin F2 alpha. Eur J Pharmacol. 2003 Nov 28;481(2-3):133-40.
The aim of this study was to determine the role of Cl (-) channel activation in prostaglandin F (2 alpha)-stimulated aortic contraction and in membrane depolarization during stimulation with prostaglandin F (2 alpha) in an aortic smooth muscle cell line (A7r5). The Cl (-) channel antagonists 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), indanyloxyacetic acid-94 (IAA-94) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) were found to decrease (P <0.05) the maximum tension generated by rat thoracic aortic segments during stimulation with prostaglandin F (2 alpha) and to shift the concentration-response relationship to the right. In the presence of Nifedipine and Cesium, rat aorta-derived A7r5 smooth muscle cells demonstrated outwardly rectifying voltage-dependent currents that were inhibited by NPPB, IAA-94 and DIDS. Both inward and outward currents were enhanced (P <0.05) following addition of prostaglandin F (2 alpha) (4 micromol/l, final concentration) to the bath solution and this increase was completely inhibited by NPPB. In the absence of Cesium, the addition of prostaglandin F (2 alpha) (4 micromol/l) to the extracellular bath solution either depolarized or hyperpolarized the cell membrane depending on the equilibrium potential for Cl (-) ions. Our results indicate that altered Cl (-) conductance is an important mechanism mediating membrane depolarization and contraction of aortic smooth muscle cells during stimulation with prostaglandin F (2 alpha). Given the significant role that prostaglandin F (2 alpha) and its biologically active isomers, the F (2) isoprostanes, play in the control of vascular tone during hypoxic and oxidative stress in the systemic circulation, alterations in Cl (-) channel function and expression may represent an important mechanism in the pathogenesis of abnormal blood flow regulation in disease states. |
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