Evidence for a role of NA+/H+ exchange in platelets activated with calcium-ionophore A 23187.
We have investigated the release of protons from human platelets and platelet aggregation induced by the calcium ionophore, A 23187. Addition of the ionophore to suspensions of washed platelets resulted in fast liberation of H+. In the presence of 0.2 mM amiloride, a potent inhibitor of Na+/H+ countertransport, the amount of protons liberated was decreased by 50% and was further reduced to about 10% by 1 mM amiloride. Similar inhibition of H+-release was observed after decreasing Na+ in the incubation medium. Both results suggest that increasing internal Ca2+ by the ionophore induces Na+/H+ exchange in human platelets. Platelet aggregation could be induced by adding the ionophore to the platelet suspension. This aggregation was inhibited by amiloride, at least when induced by low ionophore concentrations. The results suggest that stimulation of Na+/H+ exchange, and the concomitant increase in intraplatelet pH, are important mechanisms in platelet activation.
D000584:Amiloride / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology*; D002352:Carrier Proteins / Q000097:blood*; D002794:Choline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers; D013997:Time Factors
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D000001:Calcimycin; D000584:Amiloride; D002794:Choline