Timolol may inhibit aqueous humor secretion by cAMP-independent action on ciliary epithelial cells

CW McLaughlin, D Peart, RD Purves… - … of Physiology-Cell …, 2001 - journals.physiology.org
CW McLaughlin, D Peart, RD Purves, DA Carré, K Peterson-Yantorno, CH Mitchell
American Journal of Physiology-Cell Physiology, 2001journals.physiology.org
The β-adrenergic antagonist timolol reduces ciliary epithelial secretion in glaucomatous
patients. Whether inhibition is mediated by reducing cAMP is unknown. Elemental
composition of rabbit ciliary epithelium was studied by electron probe X-ray microanalysis.
Volume of cultured bovine pigmented ciliary epithelial (PE) cells was measured by
electronic cell sizing; Ca2+ activity and pH were monitored with fura 2 and 2′, 7′-bis (2-
carboxyethyl)-5 (6)-carboxyfluorescein, respectively. Timolol (10 μM) produced similar K and …
The β-adrenergic antagonist timolol reduces ciliary epithelial secretion in glaucomatous patients. Whether inhibition is mediated by reducing cAMP is unknown. Elemental composition of rabbit ciliary epithelium was studied by electron probe X-ray microanalysis. Volume of cultured bovine pigmented ciliary epithelial (PE) cells was measured by electronic cell sizing; Ca2+ activity and pH were monitored with fura 2 and 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, respectively. Timolol (10 μM) produced similar K and Cl losses from ciliary epithelia in HCO/CO2 solution but had no effect in HCO/CO2-free solution or in HCO/CO2 solution containing the carbonic anhydrase inhibitor acetazolamide. Inhibition of Na+/H+ exchange by dimethylamiloride in HCO/CO2 solution reduced Cl and K comparably to timolol. cAMP did not reverse timolol's effects. Timolol (100 nM, 10 μM) and levobunolol (10 μM) produced cAMP-independent inhibition of the regulatory volume increase (RVI) in PE cells and increased intracellular Ca2+ and pH. Increasing Ca2+ with ionomycin also blocked the RVI. The results document a previously unrecognized cAMP-independent transport effect of timolol. Inhibition of Cl/HCO exchange may mediate timolol's inhibition of aqueous humor formation.
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