Beta-blocking agents inhibit Na+K+ATPase in cultured corneal endothelial and epithelial cells

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 less than .001). Timolol maleate also inhibited the activity of Na+K+ATPase in epithelial cells in the concentration range from 10(-12) to 10(-4) M (16-68%). The inhibition was significant to the p = .002 level at concentrations greater than 10(-11) M. Although the data suggested that both drugs caused inhibition of Mg+2ATPase through the same concentration ranges, none of the values were statistically different compared to the controls. This study may point to a minor inhibition of the deturgescent pump with the use of these agents. It may also indicate caution for usage in patients with metabolically stressed corneas.