The role of intracellular pH and Ca++ on arachidonic acid metabolism in human platelets.

High concentrations of ionomycin induced arachidonic acid metabolism, while its magnitude appeared to be poorly correlated with the increase in intracellular Ca++ induced by ionomycin. Intracellular pH elevation had no direct effect on arachidonic acid release. On the other hand, the elevation in intracellular pH potentiated arachidonic acid release induced by low concentrations of ionomycin, and appeared to increase the sensitivity to Ca++ of the arachidonic acid releasing mechanism. pHi fixed at low values suppressed the formation of the product of the cyclooxygenase pathway more severely than that of 12-lipoxygenase in platelet activation induced by receptor-mediated agonists. Inhibition of the Na+/H+ exchanger, which participates in intracellular pH elevation, reduced the production of arachidonic acid metabolites, with a more profound effect on the product of the cyclooxygenase pathway. The findings suggest that intracellular Ca++ and pH act synergistically to activate the arachidonic acid releasing mechanism in platelets, and that pH also regulates the activity of the cyclooxygenase pathway.