PLATELET ACTIVATING FACTOR-INDUCED AGGREGATION OF CALF PLATELETS - APPARENT POSITIVE COOPERATIVITY IN THE KINETICS AND NON COMPETITIVE-INHIBITION BY DILTIAZEM
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Date
1992
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JOURNAL OF BIOSCIENCES
Abstract
Aggregation of calf platelets by platelet activating factor was characterized by a spectrophotometric method. The aggregation kinetics of both platelet-rich plasma and purified platelets showed concave up double-reciprocal plots and linear Hill plots with h > 1 (1.7 +/- 0.2) consistent with positive cooperativity. Comparable values of maximum rates of aggregation (R) were obtained with platelet-rich plasma (0.25 +/- 0.08) and purified platelets (0.28 +/- 0.18) but the half-maximal saturation concentration (S0.5) differed greatly between platelet-rich plasma (6 +/- 3 nM) and purified platelets (0.28 +/- 0.18 nM). An Arrhenius activation energy of 21 +/- 2 kcal/mol was found for aggregation of purified platelets. Diltiazem was inhibitory with half-maximal inhibitory concentration (I0.5) of 4-mu-M but the inhibition was not competitive. Diltiazem inhibited rates but not the extent of shape-change. The receptor-antagonist and sulphydryl reagent N-ethylmaleimide and the platelet antagonistic omega-3-fatty acid, 5,8,11,14,17-eicosa pentaenoic acid, inhibited both rates and extent of shape-change reactions and inhibited aggregation competitively (I0.5 approximately 5-mu-M). Eicosa pentaenoic acid at > 25-mu-M could abolish shape-change reactions and at 50-mu-M served as an activator of platelets and the activation was enhanced by aspirin (1 mM). Although N-ethylmaleimide at > 20-mu-M could also induce platelet activation it failed to induce aggregation and aspirin had no effect on the shape-change reactions induced by it.
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Life Sciences & Biomedicine - Other Topics
Citation
17 ,2;141-149