The Effect Of A Completely Synthesized Platelet-Activating Factor (S-PAF), 1-0-Octadecyl-2-Acetyl-Sn-Glyceryl-3-Phos-Phorylcholine, On Mammalian Platelets

Studies Were Undertaken To Examine The Action Of S-Paf On Mammalian Platelets And Its Modification By A Variety Of Agents Known To Alter Platelet Aggregation. Racemic S-Paf Aggregated Washed Platelets Of Dogs, Humans, Rabbits And Guinea Pigs But Not Rats With Ec₅₀ Values In The Nm And Sub-Nm Range. Albumin Was Necessary For The Stabilization Of Dilute Stock Solutions Of S-Paf But, Above 0.3% Final Concentration, Inhibition Of The Response Was Noted. In Prp, The Activity Of S-Paf Was Reduced Further To About 1/10 The Activity Seen In Buffered Solutions. Using Canine Platelets For Most Of The Remaining Studies It Was Noted That The Activity Of The S-Paf Resided In The Natural R Isomer. The Action Of S-Paf On Washed Platelets Could Be Inhibited By Camp Phosphodiesterase Inhibitors, Ibmx And Ro 20-1724, To The Extent Of 100% And 30%, Respectively, At 100 μM. The Activator Of Adenylate Cyclase, Pge₁, Also Inhibited The S-Paf Effect Completely But With As Little As 1 μM. Colchicine, However, Was Inactive. Surprisingly, The Lipoxygenase (Lo) Inhibitors Etya (5,8,11,14-Eicoso- Tetraynoic Acid) And Ndga (Nordihydroguaiaretic Acid) At 100 μM Completely Blocked S-Paf Action While The Cyclooxygenase (Co) Inhibitor, Indomethacin, At The Same Concentration Reduced It By Only 50%. The Effect Of The Lo Inhibitors Was Reduced In 0.3% Albumin And Completely Prevented In Prp. The Action Of The Co Inhibitor, Indomethacin, Was Not Altered By The Presence Of Protein. Although The Action Of Indomethacin On S-Paf Disappeared At 10 μM, It Still Completely Blocked The Effects Of Arachidonic Acid (Aa) In Prp. Taken Collectively, These Data Suggest That S-Paf Can Be Blocked By Agents Which Are Able To Elevate Camp Or Inhibit The Lo Pathway Of Aa Metabolism.