Differential effects of ganodermic acid S on the thromboxane A2-signaling pathways in human platelets.
Ganodermic acid S (GAS) [lanosta-7,9(11),24-triene-3beta,15alpha-diacetoxy-26-oic acid], isolated from the Chinese medicinal fungus Ganoderma lucidum (Fr.) Karst (Polyporaceae), exerted a concentration-dependent inhibition on the response of human gel-filtered platelets (GFP) to U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F2alpha), a thromboxane (TX) A2 mimetic. GAS at 2 microM inhibited 50% of cell aggregation. GAS at 7.5 microM inhibited 80% of Ca2+ mobilization, 40% of phosphorylation of myosin light chain and pleckstrin, 80% of alpha-granule secretion, and over 95% of aggregation. GAS also strongly inhibited U46619-induced diacylglycerol formation, 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 integrin alphaIIbbeta3 and aggregation. However, GAS did not inhibit U46619-induced platelet shape change or the inhibitory effect of U46619 on the prostaglandin E1-evoked cyclic AMP level in GFP. It is concluded that GAS inhibits platelet response to TXA2 on the receptor-Gq-phospholipase Cbeta1 pathway, but not on the receptor-G1 pathway.
Su
C Y
CY
Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Shiao
M S
MS
Wang
C T
CT
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D020940:Reishi; D015398:Signal Transduction / Q000187:drug effects*; D013928:Thromboxane A2 / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D004365:Drugs, Chinese Herbal; D014662:Vasoconstrictor Agents; C061905:ganodermic acid S; D007810:Lanosterol; D016718:Arachidonic Acid; D014443:Tyrosine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium