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(Hypertension. 2000;35:103.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Tyrosine Phosphorylation of Human Platelet Plasma Membrane Ca²⁺-ATPase in Hypertension

K. A. Blankenship; C. B. Dawson; G. R. Aronoff; W. L. Dean

From the Department of Biochemistry and Molecular Biology and the Department of Medicine (G.R.A.), University of Louisville School of Medicine, Louisville, Ky.

Abstract—Intracellular Ca²⁺ is increased in the platelets of hypertensive individuals. Previously, we demonstrated that platelet plasma membrane Ca²⁺-ATPase (PMCA) activity inversely correlates with diastolic blood pressure and that inhibition of this Ca²⁺ pump could explain the elevation of cytosolic Ca²⁺ in hypertension. More recently, we discovered that PMCA is phosphorylated on tyrosine residues during thrombin-stimulated platelet aggregation and that this phosphorylation causes inhibition of PMCA activity. In the present work, we tested the hypothesis that tyrosine phosphorylation of PMCA in hypertensive patients could account for the observed inhibition of the Ca²⁺ pump. Platelets were obtained from untreated hypertensive and normotensive volunteers. PMCA was immunoprecipitated from solubilized platelets, and tyrosine phosphorylation was quantified by chemiluminescence of immunoblots treated with anti-phosphotyrosine. PMCA content was measured on the same immunoblots by stripping and reprobing with anti-PMCA. Phosphorylation was reported as normalized phosphotyrosine chemiluminescence per nanogram PMCA (mean±SE). The average PMCA tyrosine phosphorylation for 15 normotensive subjects was 0.53±0.09, whereas the average for 8 hypertensive individuals was 1.82±0.25 (P<0.0005, Mann-Whitney U test). Age, gender, and systolic blood pressure did not correlate with PMCA phosphorylation. These results suggest that PMCA in platelets of hypertensive individuals is inhibited because of tyrosine phosphorylation, resulting in increased platelet intracellular Ca²⁺, hyperactive platelets, and increased risk of heart attack and stroke.

Key Words: Ca²⁺-transporting ATPase • calcium • hypertension, essential • phosphorylation • platelets

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