MALONDIALDEHYDE FORMATION IN RAT PLATELET-RICH PLASMA .2. MODIFICATION OF THE REACTION-KINETICS BY ASPIRIN AND INDOMETHACIN INVITRO

  • 1 January 1980
    • journal article
    • research article
    • Vol. 44  (2) , 52-55
Abstract
The type of inhibition and the relative potency of aspirin and indomethacin on rat platelet malondialdehyde (MDA) formation were investigated in an in vitro system. Both drugs inhibited production of MDA after platelet stimulation with either thrombin (10 or 25 NIH u/ml) or sodium arachidonate (0.5-2.25 mM). Inhibition by both drugs was concentration-dependent, was partially removed when platelet-rich plasma was diluted with platelet-poor plasma, was much stronger when either drug was preincubated with platelets for 10 min than for 1 min and was apparently competitive when analyzed by Dixon plots (1/V versus inhibitor concentrations). Both aspirin and indomethacin may inhibit in vitro cyclooxygenase activity in citrate platelet-rich plasma by a similar, if not identical, partially reversible mechanism, not involving - in a 1st step - covalent binding of either drug to enzyme. A scheme of the interaction of both drugs with cyclooxygenase is presented which also takes into account the irreversible acetylation of the enzyme occurring after longer incubation times with aspirin.