Potentiation of ganodermic acid S on prostaglandin E(1)-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) E(1). GAS at <20 microM did not show any significant change of basal cyclic AMP level in gel-filtered platelets. However, GAS potentiated the PGE(1)-evoked cyclic AMP level in a bell-shaped, concentration-dependent manner. The agent at 7.5 microM enhanced the level up to 1.8-fold of that evoked by PGE(1) alone. Collagen did not inhibit the PGE(1)-induced cyclic AMP level in platelets pretreated with GAS at 6 to 7.5 microM. In the presence of 7.5 microM GAS, the agent enhanced the inhibition of PGE(1) on platelet response to collagen in: phosphorylation of myosin light chain and pleckstrin; alpha-granule secretion; cell aggregation and protein-tyrosine phosphorylation. In addition, the agent along with PGE(1) almost abolished the dense-granule secretion and thromboxane (TX) B(2) formation. The results suggest that GAS played an additional role in potentiating the PGE(1)-induced cyclic AMP synthesis. GAS and PGE(1) inhibited additively the platelet response to collagen.
Su
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Department of Life Science, National Tsing Hua University, 300, Hsinchu, Taiwan.
Shiao
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Wang
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D000527:Alprostadil / Q000494:pharmacology*; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D020940:Reishi / Q000737:chemistry
D010975:Platelet Aggregation Inhibitors; C061905:ganodermic acid S; D007810:Lanosterol; D003094:Collagen; D000242:Cyclic AMP; D000527:Alprostadil