Blockade by metal complexing agents and by catalase of the effects of arachidonic acid on platelets: relevance to the study of anti-inflammatory mechanisms.
Metal-chelating agents inhibited platelet aggregation and the accompanying generation of rabbit aorta contracting and PG-like activities, when platelets were challenged with arachidonic acid. Inhibition required the presence of the chelating agents in the medium, and was insured by reagents avid for free or protein-bound copper. Catalase also prevented aggregation and generation of pharmacologically active substances; its activity was reversed by aminothiol agents and by Cu2+ and Zn2+, shown previously to potentiate the platelet effects of arachidonic acid. Inhibition by indomethacin was not prevented by amino-thiol drugs nor by Cu2+ or Zn2+. The catalase-induced inhibition was not affected by scavenging of thiol groups; this rules out, as a mechanism of action of catalase, the increased destruction of popoperoxides by glutathione peroxidase, which requires reduced glutathione as hydrogen donor. The results are compatible with the hypothesis that the agent that mediates platelet aggregation by arachidonic acid is a popoperoxide, requiring the presence either of H2O2 or of a similarly catalase-sensitive substance to be generated.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002374:Catalase / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D002729:Chloromercuribenzoates / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D013270:Stomach / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D001386:Azides; D002614:Chelating Agents; D002729:Chloromercuribenzoates; D000244:Adenosine Diphosphate; D003300:Copper; D002374:Catalase; D015032:Zinc; D003545:Cysteine; D005033:Ethylmaleimide; D000640:Amitrole