Effects of organic and inorganic Ca antagonists on rat platelet arachidonic acid metabolism in the presence of Ca2+, Sr2+ and Ba2+.
The effects of Ca-antagonists on the thrombin-induced mobilization of radiolabeled arachidonate preincorporated into rat platelets as well as the subsequent formation of labeled cyclooxygenase and lipoxygenase products were analyzed in the presence of either Ca2+ or Ca2+-substitutes, Sr2+ and Ba2+. Results indicate that following thrombin stimulation (0.2 U/ml) in the presence of Ca2+, nitrendipine (Nit), Cd2+ or Mn2+ reduced the release of arachidonate and the biosynthesis of thromboxane B2. Inhibition of arachidonic acid release and metabolism were also obtained by both Nit and Cd2+ in the presence of Sr2+ and Ba2+. Results from studies with a semi-purified phospholipase A2 fraction prepared from rat platelets indicated that the activity was almost unaffected by Nit or Cd2+. From these findings, we concluded that inhibition of platelet-induced release and metabolism of arachidonic acid by the Ca-antagonists tested require intact platelets. These data support the hypothesis of an interaction of these agents at an unknown surface membrane level.
Blache
D
D
Institut National de la Santé et de la Recherche Médicale, Unité 63, Laboratoire de Physiologie Vasculaire Lyon-Bron, France.
Ciavatti
M
M
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood* / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009568:Nitrendipine / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D013324:Strontium / Q000494:pharmacology*; D013917:Thrombin / Q000502:physiology
D001095:Arachidonic Acids; D002413:Cations, Divalent; D002104:Cadmium; D001464:Barium; D016718:Arachidonic Acid; D008345:Manganese; D009568:Nitrendipine; D013917:Thrombin; D002118:Calcium; D013324:Strontium