Differential effects of ganodermic acid S on the thromboxane A2-Signaling pathways in human platelets

• Published in: Biochemical pharmacology 1999-08, Vol.58 (4), p.587-595
• Main Authors: SU, C.-Y, SHIAO, M.-S, WANG, C.-T
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Adenylyl Cyclase Inhibitors; Adenylyl Cyclases - metabolism; Arachidonic Acid - metabolism; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood. Blood coagulation. Reticuloendothelial system; Calcium - metabolism; Cyclic AMP - metabolism; Drugs, Chinese Herbal - chemistry; Humans; Lanosterol - analogs & derivatives; Lanosterol - pharmacology; Medical sciences; Pharmacology. Drug treatments; Phosphorylation; Platelet Aggregation - drug effects; Reishi; Signal Transduction - drug effects; Thromboxane A2 - metabolism; Tyrosine - metabolism; Vasoconstrictor Agents - pharmacology
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(99)00136-7

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.