Differential effects of ganodermic acid S on the thromboxane A(2)-signaling pathways in human platelets

Ganodermic acid S (GAS) [lanosta-7,9(11),24-triene-3 beta,15 alpha-diacetox y-26-oic acid], isolated from the Chinese medicinal fungus Ganoderma lucidu m (Fr.) Karst (Polyporaceae), exerted a concentration-dependent inhibition on the response of human gel filtered platelets (GFP) to U46619 (9,11-dideo xy-9 alpha,11 alpha-methanoepoxyprostaglandin F-2 alpha), a thromboxane (TX ) A(2) mimetic. GAS at 2 mu M inhibited 50% of cell aggregation. GAS at 7.5 mu M inhibited 80% of Ca2+ mobilization, 40% of phosphorylation of myosin light chain and pleckstrin, 80% of cw-granule secretion, and over 95% of ag gregation. GAS also strongly inhibited U46619 induced diacylglycerol format ion, arachidonic acid release, and TXB2 formation. An immunoblotting study of protein-tyrosine phosphorylation showed that GAS inhibited the formation of phosphotyrosine proteins at the steps involving the engagement of integ rin alpha(IIb)beta(3) and aggregation. However, GAS did not inhibit U46619- induced platelet shape change or the inhibitory effect of U46619 on the pro staglandin El evoked cyclic AMP level in GFP. It is concluded that GAS inhi bits platelet response to TXA(2) on the receptor-G(q)-phospholipase C beta 1 pathway, but not on the receptor-G, pathway. (C) 1999 Elsevier Science In c.