Stimulation of calcium uptake by 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) in rabbit platelets: possible involvement of the lipoxygenase pathway.
1-Alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) induces an increase of Ca2+ uptake in rabbit platelets. This process depends upon the extracellular concentration of Ca2+ with the maximum stimulation occurring at 1-3 mM; uptake under these conditions is blocked by verapamil, a calcium-entry blocker. Increase of calcium uptake by the bioactive phospholipid was independent of ADP-induced platelet responses and of metabolites of arachidonic acid metabolism formed through the cyclooxygenase pathway. However, mepacrine, p-bromophenacyl bromide, eicosatetraynoic acid, and nordihydroguaiaretic acid significantly or totally inhibited the stimulation of Ca2+ uptake by 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine. When arachidonic acid was given sufficient time to be metabolized to other products by the platelets, stimulation of Ca2+ uptake also occurred. Arachidonic acid and platelet-activating factor did not produce an additive or synergistic effect. Our data suggest that a metabolite(s) generated from arachidonic acid through the lipoxygenase pathway may be the mediator(s) responsible for the action of platelet-activating factor in the induction of increased Ca2+ uptake in rabbit platelets.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology / Q000502:physiology*; D001693:Biological Transport, Active / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D014700:Verapamil; D002118:Calcium; D007213:Indomethacin