Browsing by Author "THOMAS, A"

Now showing 1 - 5 of 5
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    A MOLECULAR MECHANISM FOR THE DITHIOTHREITOL-MEDIATED PLATELET-AGGREGATION
    (THROMBOSIS AND HAEMOSTASIS, 1987) JAMALUDDIN, MP; SREEDEVI, C; THOMAS, A; KRISHNAN, LK
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    AJOENE INHIBITION OF PLATELET-AGGREGATION - POSSIBLE MEDIATION BY A HEMOPROTEIN
    (BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988)
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    COMPETITIVE-INHIBITION OF HYDROGEN PEROXIDE-INDUCED AGGREGATION OF CALF PLATELETS BY PROSTAGLANDIN H-2 THROMBOXANE A2 RECEPTOR LIGANDS
    (JOURNAL OF BIOSCIENCES, 1992) JAMALUDDIN, M; THOMAS, A
    Hydrogen peroxide (H2O2)-induced aggregation of calf platelets and its modification by agents with specific properties were characterized employing a spectrophotometric assay. An Arrhenius activation energy of 20 +/- 1 kcal/mol was found in the temperature range of 25-degrees-36-degrees-C. Rate inhibition occurred on either side of this temperature range, and under anaerobic conditions. Exogenous Ca2+ ions were not required but Ca2+ ions, at 1 mM-concentration, optimally increased rates and extent of aggregation at suboptimal H2O2 concentrations but only extent of aggregation at optimal H2O2 concentrations. Ba2+, Sr2+, Cd2+, Mn2+ and Ni2+ ions (1 mM) and Zn2+, Pb2+ and Hg2+ ions (10-mu-M) were inhibitory. The cyclo-oxygenase inhibitor, indomethacin (10-30-mu-M) exerted only mild inhibition by a competitive mechanism. Another cyclooxygenase inhibitor, aspirin, functioned to increase aggregation. Ligands acting directly at the prostaglandin H2/thromboxane A2 receptor (5Z, 9, 11, 13E, 15(S) 15-hydroxy 9(11) epoxy methano prosta 5, 13-dien-1-oic acid, pinane thromboxane A2, arachidonic acid, eicosapentaenoic acid, and N-ethylmaleimide) functioned as competitive inhibitors. Another platelet-activating sulphydryl reagent, thimerosal, also inhibited competitively while the protein kinase C inhibitor, sphingosine, and the protein kinase C modulator, Zn2+ ions, inhibited by different mechanisms. The results indicate direct action of H2O2 at the prostaglandin H2/thromboxane A2 receptor, possibly its sulphydryls, to activate the protein kinase C pathway, independently of cyclo-oxygenase products. The results underscored the power of the kinetic approach for investigating mechanisms of platelet activation.
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    PLATELET ACTIVATING FACTOR-INDUCED AGGREGATION OF CALF PLATELETS - APPARENT POSITIVE COOPERATIVITY IN THE KINETICS AND NON COMPETITIVE-INHIBITION BY DILTIAZEM
    (JOURNAL OF BIOSCIENCES, 1992) JAMALUDDIN, M; THOMAS, A
    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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    SPECTROPHOTOMETRIC PLATELET-AGGREGATION ASSAY TO MEASURE SINGLE PLATELET DISAPPEARANCE - AN EVIDENCE
    (CURRENT SCIENCE, 1987) SREEDEVI, C; THOMAS, A; JAMALUDDIN, M