Effect of Sodium Fluoride on Intracellular pH in Human Platelets

Abstract

Na⁺/H⁺ exchangers mediate intracellular pH ([pH] i) in various preparations containing platelets. In other cells C kinase, cyclic AMP, Ca²⁺, and guanine nucleotide proteins (G-proteins) are thought as the possible passway, but the mechanism is not clear in platelets. It is known that sodium fluoride (NaF) activates G-proteins and NaF itself induces platelet aggregation. This time, we have investigated whether NaF induced changes in [pH]i to make sure of regulation of G-proteins for Na⁺/H⁺ exchangers, comparing changes in the intracellular calcium ion concentration ([Ca²⁺] i), C kinase and cyclic AMP. NaF caused platelet aggregation through the elevation of [Ca²⁺] i. Stimulation of thrombin resulted in increase in [pH] i through the elevation of [Ca²⁺] i, but NaF failed to raise the [pH] i, and a low concentration of NaF, which did not cause aggregation, inhibited thrombin-induced increase in [pH] i but did not inhibit thrombin-induced increase in [Ca²⁺] i, C kinase activation or cyclic AMP. These results suggest that NaF has an inhibitory effect on Na⁺/H⁺ exchangers via G-proteins and that an increase in [pH]i is not needed for an increase in [Ca²⁺] i.