Predominant inhibition of ganodermic acid S on the thromboxane A₂- dependent pathway in human platelets response to collagen

Ganodermic acid S (GAS), a membrane acting agent, exerts multiple effects on human platelet function (C.N. Wang et al. (1991) Biochem. J. 277, 189-197). The study reported how GAS affected the response of human gel- filtered platelets (GFP) to collagen. The agent inhibited cell aggregation by prolonging lag and shape change periods and decreasing the initial cell aggregation rate. However, the inhibitory efficiency was less than its inhibition on GFP response to U46619, a thromboxane (TX) A₂ mimetic. In the agent-effect on biochemical events, GAS effectively inhibited Ca²⁺ mobilization, phosphorylation of myosin light chain, dense granule secretion and TXB₂ generation. The inhibitions might originate from blocking Ca²⁺ mobilization of the TXA₂-dependent pathway. GAS partially decreased the phosphorylation of most phosphotyrosine proteins from early activation to the integrin α(IIb)β₃-regulated steps. The agent did not affect the phosphorylation of three proteins at the steps regulated by integrin α(IIb)β₃. The results suggest that GAS inhibits the collagen response predominantly on the TXA₂-dependent signaling, and the tyrosine kinase- dependent pathway in collagen response plays a major role in aggregation.