Timolol may inhibit aqueous humor secretion by cAMP-independent action on ciliary epithelial cells |
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Authors: | McLaughlin C W Peart D Purves R D Carré D A Peterson-Yantorno K Mitchell C H Macknight A D Civan M M |
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Institution: | Department of Physiology, University of Otago Medical School, Dunedin, New Zealand. |
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Abstract: | The -adrenergic antagonisttimolol reduces ciliary epithelial secretion in glaucomatous patients.Whether inhibition is mediated by reducing cAMP is unknown. Elementalcomposition of rabbit ciliary epithelium was studied by electron probeX-ray microanalysis. Volume of cultured bovine pigmented ciliaryepithelial (PE) cells was measured by electronic cell sizing;Ca2+ activity and pH were monitored with fura 2 and2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, respectively. Timolol (10 µM) produced similar K and Cl losses fromciliary epithelia in HCO /CO2 solutionbut had no effect in HCO /CO2-free solution or in HCO /CO2 solutioncontaining the carbonic anhydrase inhibitor acetazolamide. Inhibitionof Na+/H+ exchange by dimethylamiloride inHCO /CO2 solution reduced Cl and Kcomparably to timolol. cAMP did not reverse timolol's effects. Timolol(100 nM, 10 µM) and levobunolol (10 µM) produced cAMP-independentinhibition of the regulatory volume increase (RVI) in PE cells andincreased intracellular Ca2+ and pH. IncreasingCa2+ with ionomycin also blocked the RVI. The resultsdocument a previously unrecognized cAMP-independent transport effect oftimolol. Inhibition of Cl /HCO exchangemay mediate timolol's inhibition of aqueous humor formation. |
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