NONSTEROIDAL ANTIINFLAMMATORY DRUGS ALTER CHLORIDE AND FLUID TRANSPORT IN BOVINE RETINAL-PIGMENT EPITHELIUM

Nonsteroidal anti-inflammatory drugs (NSAIDs) were added to the soluti ons bathing the apical membrane of bovine retinal pigment epithelium ( RPE)-choroid explants. For example, niflumic acid (100 mu M) depolariz ed the basolateral membrane voltage (V-B) by similar to 12 mV, increas ed transepithelial potential by 4.5 mV, decreased intracellular Cl act ivity by 13 mM, decreased transepithelial resistance by 17 Omega . cm( 2), and increased the ratio of apical to basolateral membrane resistan ce nearly threefold. All of these changes are consistent with an incre ase in basolateral membrane Cl conductance. In addition, niflumic acid caused intracellular Ca concentration to decrease by 16 nM and fluid transport rate to increase by 1.5 mu l . cm(-2) . h(-1). Flufenamic ac id, which is structurally very similar to niflumic acid, had the oppos ite effects on membrane voltage and resistance. Basal application of t he Cl channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid or current clamping V-B to the reversal potential for Cl practically abolished the niflumic acid response. The niflumic acid response was u naffected by protein kinase inhibitors. These results suggest that cer tain NSAIDs can directly alter Cl conductance in the bovine RPE, appar ently independently of cyclooxygenase inhibition.