Abstract
alpha-Thrombin, phorbol esters (PMA) and 1,2-diacylglycerol (DAG), three activators of the amiloride-sensitive Na+/H+ exchange in human platelets, rapidly increase the intracellular pH and the level of phosphorylation of the Na+/H+ exchange protein (NHE1). This stimulatory effect is suppressed by staurosporine, a potent kinase inhibitor, and increased by okadaic acid, a potent inhibitor of phosphatase 1 and 2A. The modulations of NHE1 phosphorylation by these factors correlate well with their effects on platelet pH. Thus, we conclude that in platelets (i) Na+/H+ exchange is mediated by NHE1, and (ii) platelet activating agents stimulate NHE1 via the modulation of the kinase/phosphatase equilibrium.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / pharmacology
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Blood Platelets / drug effects
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Blood Platelets / metabolism*
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Carrier Proteins / blood*
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Diglycerides / pharmacology
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Ethers, Cyclic / pharmacology
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Humans
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Hydrogen-Ion Concentration
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Okadaic Acid
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Phosphorylation
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Protein Kinase Inhibitors
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Protein Phosphatase 1
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Sodium-Hydrogen Exchangers
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Staurosporine
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Tetradecanoylphorbol Acetate / pharmacology*
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Thrombin / pharmacology*
Substances
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1,2-diacylglycerol
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Alkaloids
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Carrier Proteins
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Diglycerides
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Ethers, Cyclic
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Protein Kinase Inhibitors
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Sodium-Hydrogen Exchangers
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Okadaic Acid
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Phosphoprotein Phosphatases
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Protein Phosphatase 1
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Thrombin
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Staurosporine
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Tetradecanoylphorbol Acetate