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M. Shimura, H. Tomita, K. Yasuda, K. Kashiwagi, M. Tamai; The Effects of Unoprostone on Ca2+ Release-Activated Ca2+ Channels in Cultured Monkey Ciliary Smooth Muscle Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4387.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the effect of unoprostone isopropyl (UP) on Ca2+ release-activated Ca2+ (CRAC) channels in cultured monkey ciliary smooth muscle (CSM) cells. It is accepted that suppression of intracellular Ca2+ concentration ([Ca2+]i) in the contractile elements of the outflow pathway plays a key role in the increase of aqueous outflow. The mechanism of reduction of intraocular pressure (IOP) induced by unoprostone is still debated, however there have been some reports that UP suppress the Ca2+ entry through some types of Ca2+ channels in the plasma membrane. Methods: Monkey CSM cells were grown in monolayer cell cultures. To measure the alteration of intracellular Ca2+ concentration ([Ca2+]i), CSM cells were labelled with Fluo-3 AM, as a calcium indicator, for 30 min at 25° C, and imaged with confocal laser scanning microscope.UP and metabolites (M1) were first dissolved in dimethyl sulfoxide (DMSO) at a concentration of 10 mM. Results: After depletion of intracellular Ca2+ stores with 1 µM thapsigargin, and 1 mM EGTA containing Ca2+-free external solution for 5 min, exposure of 2 mM Ca2+-containing external solution induced sudden increase of [Ca2+]i. 10 µM 2-APB, a specific CRAC channel inhibitor, suppressed this increase. Both 100 µM of UP and M1 also decreased the CRAC current with 68.3 ± 11.5% (UP), 71.1 ± 16.5%, respectively (n=5). 1%DMSO containing solution did not affect the CRAC current. Conclusions: This study presents that CRAC channel is observed in the cultured CSM cells, and the increase of [Ca2+]i through CRAC channel was reduced by unoprostone isopropyl. CRAC channel is known to be activated during regulatory volume decrease. Thus, unoprostone may suppress volume tension of CSM cells which leads the increase of aqueous outflow and subsequent reduction of IOP.
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