Chloroquine: A multipotent inhibitor of human platelets in vitro

Chloroquine inhibited human platelet aggregation in vitro both at receptor- and nonreceptor-operated stimuli. The inhibition was dose-dependent, recor ded on isolated platelets as well as in platelet-rich plasma, and followed the rank order of stimuli: adrenaline (second phase)>phorbol 12-myristate 1 3 acetate>adenosine diphosphate>adrenaline (first phase)>thrombin>calcium i onophore A23187. In thrombin-activated platelets, chloroquine decreased in a dose-dependent manner phospholipase A(2)-induced arachidonic acid liberat ion from membrane phospholipids, malondialdehyde formation (a marker of mem brane phospholipid peroxidation), and thromboxane generation, considered th e most potent autoaggregatory agent. Chloroquine only slightly altered the arachidonic acid cascade of platelets stimulated with A23187 and phorbol 12 -myristate 13 acetate. Histamine formation and liberation induced with thro mbin and A23187 were not affected by chloroquine. On the other hand, thromb in-stimulated serotonin secretion was significantly decreased with chloroqu ine in the concentration of 10 mu mol/L. This indicated that chloroquine mi ght interfere with stimulated secretion from platelets. The results suggest that chloroquine inhibited activated platelets: first, intracellularly; se cond, in a close relationship to the intraplatelet Ca2+ mobile pool; and th ird, most probably at the site of platelet pbospholipase A(2) activation. ( C) 2000 Elsevier Science Ltd. All rights reserved.