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Bovine, non-pigmented, ciliary body epithelial cells were isolated and grown in culture to determine whether timolol maleate might affect the activity of their plasma membrane ATPases. The possible effects were tested in drug concentrations in a range of 5 x 10(-19) to 5 x 10(-5) M over an incubation period of 30 min at 37 degrees. Assays of specific activity showed that the drug significantly (p less than .001 for most concentrations) inhibited both Na,K-ATPase and Mg-ATPase. However, the inhibition was partially reversed in concentrations greater than 10(-6) M for Na,K-ATPase and 10(-5) M for Mg-ATPase. The latter enzyme also indicated a second partial reversal in activity at concentrations between 10(-12) and 10(-9) M. These reversals in activity suggest that more than one binding site is involved in the inhibition of both enzymes. Since Na,K-ATPase in non-pigmented, ciliary body cells is responsible for the generation of aqueous fluid and the intraocular pressure (IOP), this inhibition demonstrates a possible mechanism for the pharmacological action of timolol maleate in lowering IOP.

An effort was made to determine whether the beta-blocking agents: timolol maleate and betaxolol hydrochloride could affect the activity of the plasma membrane, transport ATPases of corneal endothelial and epithelial cells grown in culture. It was found that both agents were able to inhibit the activity of Na+K+ATPase in endothelial cells in the concentration range from 10−12 to 10−4 M (47– 77% inhibition with timolol and 24-78% inhibition with betaxolol). In concentrations of 10−9 M or greater (for betaxolol) and 10−12 M or greater (for timolol) the inhibition was highly significant (p