Dissociation between inhibition of phospholipid methylation and production of PAF-acether by rabbit platelets.
Platelet-activating-factor (PAF-acether, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is formed by and released from rabbit platelets stimulated with thrombin, with the ionophore A23187, with collagen and with the platelet-stimulating glycoprotein convulxin. We here show that 3-deazaadenosine (C3ado) and L-homocysteine (HCy), two inhibitors of platelet methylation, reduced the formation of PAF-acether and of its deacetylated product lyso-PAF-acether by rabbit platelets challenged with thrombin, under conditions where the accompanying aggregation was not significantly modified. In contrast, platelet aggregation induced by convulxin was completely and irreversibly blocked when C3ado and HCy were associated. Aggregation by thrombin was not affected by the methylation inhibitors even when ADP was scavenged and thromboxane formation was suppressed. Our results indicate that phospholipid methylation, thrombin-induced platelet aggregation and formation of PAF-acether can be dissociated. The formation of PAF-acether by rabbit platelets can be blocked by mechanisms other than inhibition of phospholipase A2, since the latter is not affected by C3ado and/or HCy.
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D003435:Crotalid Venoms / Q000494:pharmacology; D006710:Homocysteine / Q000494:pharmacology; D007700:Kinetics; D037181:Lectins, C-Type; D008745:Methylation; D010743:Phospholipids / Q000097:blood*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000096:biosynthesis*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology; D014372:Tubercidin / Q000494:pharmacology
D003435:Crotalid Venoms; D037181:Lectins, C-Type; C029271:O-deacetyl platelet activating factor; D010743:Phospholipids; D010972:Platelet Activating Factor; C018258:3-deazaadenosine; D006710:Homocysteine; C028890:convulxin; D013917:Thrombin; D014372:Tubercidin