CL CHANNEL BLOCKERS INHIBIT THE VOLUME-ACTIVATED EFFLUX OF CL AND TAURINE IN CULTURED NEURONS

The effects of the Cl channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), 1,9-dideoxyforskolin (DDF), dipyridamole, and nif lumic acid and of the polyunsaturated fatty acids arachidonic, linolen ic, and linoleic acids on regulatory volume decrease (RVD) and associa ted I-125 and [H-3]taurine fluxes in cultured rat cerebellar granule n eurons were examined. Dose-response curves of NPPB, DDF, and dipyridam ole showed 20-100% inhibition of RVD and osmolyte fluxes. Niflumic aci d was less potent, requiring 150-600 mu M to show effects of this magn itude. The polyunsaturated fatty acids (5-20 mu M) inhibited 80-90% RV D and osmolyte fluxes, with arachidonic acid exhibiting the most poten t effect. The volume-associated taurine efflux was somewhat higher in younger neurons, but the pharmacological sensitivity was essentially t he same in immature and mature cells. The effects of all tested drugs on I-125 and [H-3]taurine fluxes were remarkably similar, indicating a close pharmacological sensitivity of the transport mechanism for the two osmolytes. This is in line with the suggestion of a common pathway for the volume-associated release of Cl and amino acids functioning a s osmolytes.