This study addresses the role of the Na+/H+ exchanger (NHE) in the generation of procoagulant activity in blood platelets. It was found that monensin (simulating the action of NHE) and gramicidin (causing sodium influx without concomitant H+ efflux) produced a dose- and time-dependent increase in platelet procoagulant activity. Alkalinization of platelet cytosol by NH(4)Cl failed to evoke a procoagulant response. Collagen-induced procoagulant response was diminished in the absence of external Na+ and in the presence of EIPA (NHE inhibitor) or GF 109203X (protein kinase C inhibitor). Phorbol ester (PMA) produced a dose- and time-dependent generation of procoagulant response which was inhibited in the absence of the external Na+ and in the presence of EIPA. Platelets stimulated by collagen and PMA accumulated (22)Na+, a phenomenon inhibited in the presence of EIPA. The data indicate that development of procoagulant activity in platelets may occur as a result of Na+ influx via Na+/H+ exchanger.
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