Whikehart D R, Montgomery B, Sorna D H
Vision Science Research Center, School of Optometry, University of Alabama, Birmingham.
J Ocul Pharmacol. 1992 Summer;8(2):107-14. doi: 10.1089/jop.1992.8.107.
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.
分离出牛的非色素睫状体上皮细胞并在培养中生长，以确定马来酸噻吗洛尔是否可能影响其质膜ATP酶的活性。在37℃孵育30分钟的时间内，以5×10⁻¹⁹至5×10⁻⁵M的药物浓度测试可能的影响。比活性测定表明，该药物显著抑制（大多数浓度下p＜0.001）Na，K - ATP酶和Mg - ATP酶。然而，对于Na，K - ATP酶，浓度大于10⁻⁶M时抑制作用部分逆转；对于Mg - ATP酶，浓度大于10⁻⁵M时抑制作用部分逆转。后一种酶在10⁻¹²至10⁻⁹M的浓度下活性也出现第二次部分逆转。这些活性逆转表明，两种酶的抑制涉及不止一个结合位点。由于非色素睫状体细胞中的Na，K - ATP酶负责房水生成和眼内压（IOP），这种抑制作用证明了马来酸噻吗洛尔降低IOP药理作用的一种可能机制。
