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.
Arellano
R
R
Division of Cell Biology, Research Institute, Hospital for Sick Children, Toronto, Canada.
Grinstein
S
S
D019204:GTP-Binding Proteins / Q000378:metabolism*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D017368:Protein Prenylation; D014407:Tumor Cells, Cultured
D009240:N-Formylmethionine Leucyl-Phenylalanine; D008148:Lovastatin; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D019204:GTP-Binding Proteins; D008798:Mevalonic Acid