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Abstract #14982 Published in IGR 8-4
The effect of unoprostone isopropyl on Ca2+ release-activated Ca2+ currents in cultured monkey trabecular meshwork cells and ciliary muscle cells
Shimura M; Yasuda K; Nakzawa T; Kashiwagi KJournal of Ocular Pharmacology and Therapeutics 2006; 22: 219-226
PURPOSE: The aim of this study was to investigate the effect of unoprostone isopropyl (UF- 021) on Ca2+ release-activated Ca2+ (CRAC) currents in cultured monkey trabecular meshwork (TM) cells and to compare the inhibitory effects on CRAC in cultured monkey ciliary muscle (CM) cells. METHODS: Both TM and CM cells were isolated from monkey eyes, and each was grown in monolayer cell cultures. To measure changes in intracellular Ca2+ concentrations ([Ca2+ ]i ), both types of cells were labeled with fluo-3 acetoxymethylester (AM) as a calcium indicator for 30 min at 25 degrees C and imaged with a confocal laser scanning microscope. After depletion of the intracellular Ca2+ stores with 1 μM thapsigargin and 1 mM EGTA containing Ca2+ -free external solution, exposure to 2 mM Ca2+ -containing external solution induced a sudden increase in [Ca2+ ]i , which was defined as the CRAC current. RESULTS: In both TM and CM cells, CRAC currents were observed and were well suppressed by unoprostone-free acid (M1 metabolite). In the TM cells, 3 μM M1 metabolite suppressed the CRAC current. In contrast, in the CM cells, the CRAC current was suppressed by 100 μM M1 metabolite, but not by 10 μM or less. The half maximal inhibition concentration of M1 metabolite was 24.8±9.8 μM in TM cells and 183±30.6 μM in CM cells. CONCLUSIONS: These findings indicate that there are CRAC channels in both TM and CM cells, and the influx of [Ca2+ ]i through the CRAC channels is suppressed by M1 metabolite. The inhibitory effect of M1 metabolite on CRAC currents was more prominent in TM cells than in CM cells. Suppression of the Ca2+ influx through CRAC channels by M1 metabolite is thought to regulate muscle tone in TM and CM cells. Therefore, CRAC inhibition by M1 metabolite may contribute to reduction of intraocular pressure.
Dr. M. Shimura, Department of Ophthalmology, NTT East Japan Tohoku Hospital, and Department of Ophthalmology and Medical Sciences, Tohoku University Graduate School of Medicine, Miyagi, Japan. masahiko@oph.med.tohoku.ac.jp
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.8 Pharmacology (Part of: 3 Laboratory methods)
11.4 Prostaglandins (Part of: 11 Medical treatment)
