Potentiation of ganodermic acid S on prostaglandin E₁-induced cyclic AMP elevation in human platelets

Ganodermic acid S (GAS), isolated from the Chinese medicinal fungus Ganoderma lucidum (Fr.) Karst (Polyporaceae), exhibits inhibitory effects on platelet responses to various aggregating agonists. Our study demonstrated that GAS also participated in potentiating the response of human gel-filtered platelets to prostaglandin (PG) E₁. GAS at < 20 μM did not show any significant change of basal cyclic AMP level in gel-filtered platelets. However, GAS potentiated the PGE₁-evoked cyclic AMP level in a bell-shaped, concentration-dependent manner. The agent at 7.5 μM enhanced the level up to 1.8-fold of that evoked by PGE₁ alone. Collagen did not inhibit the PGE₁-induced cyclic AMP level in platelets pretreated with GAS at 6 to 7.5 μM. In the presence of 7.5 μM GAS, the agent enhanced the inhibition of PGE₁ on platelet response to collagen in: phosphorylation of myosin light chain and pleckstrin; α-granule secretion; cell aggregation and protein-tyrosine phosphorylation. In addition, the agent along with PGE₁ almost abolished the dense-granule secretion and thromboxane (TX) B₂ formation. The results suggest that GAS played an additional role in potentiating the PGE₁-induced cyclic AMP synthesis. GAS and PGE₁ inhibited additively the platelet response to collagen. (C) 2000 Elsevier Science Ltd.