Role of isoprenylation in intracellular pH regulation of granulocytes.

Lovastatin was used to study the role of isoprenylated GTP-binding proteins in the regulation of intracellular pH in granulocytic HL-60 cells. The cytosolic acidification that accompanies stimulation by chemoattractants was completely eliminated by lovastatin. The subsequent activation of Na+/H+ exchange was partially inhibited by the isoprenylation antagonist. In contrast, the osmotic activation of the Na+/H+ antiport was unaffected. The data indicate that the osmotically- and receptor-induced activation of the antiport utilize divergent signalling pathways. The results also provide evidence supporting the notion that cytosolic acidification by chemoattractants results from accumulation of metabolic acid generated during the respiratory burst.