European journal of pharmacology

Role of Cl- currents in rat aortic smooth muscle activation by prostaglandin F2 alpha.

PMID 14642777


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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R(+)-IAA-94, ≥98% (HPLC), solid