Pinusolide from the leaves of Biota orientalis as potent platelet activating factor antagonist

We investigated the effect of a new PAF antagonist pinusolide, isolated fro m the leaves of Biota orientalis, on PAF-induced [H-3]serotinin release fro m rabbit platelets, hypotension and vascular permeability. Pinusolide (IC50 , about 5 x 10(-6) M) inhibited specifically [H-3]serotinin release from ra bbit platelets when stimulated with PAF (5 x 10(-8) M), but showed no effec t when induced by ADP, collagen, and thrombin. It also inhibited PAF-induce d hypotension in a dose-dependent manner in rats with no effect on the hypo tension induced by acetylcholine, histamine and serotonin. The inhibitory e ffect of pinusolide on the PAF-induced vascular permeability is less specif ic than the induced hypotension. These results suggest that pinusolide may prove of therapeutic value in the treatment of hypotension and a molecular design of pinusolide analogues may provide the possibility of a new PAF spe cific antagonists.