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 Call 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 132- Inhibition of arachidonic acid release and metabolism were also obtained by both Nit and Cd2+ in the presence of Sr2+ and Bat+. 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.Abbreviations AA Arachidonic Acid - 5-HT 5-hydroxy-tryptamine - HETE 12-hydroxyeicosatetraenoic acid - HHT 12-hydroxy-heptadecanoic acid - HHT Nitrendipine - TXB₂ Thromboxane B₂