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.
