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

Chen Yi Su, Ming Shi Shiao, Cheng Teh Wang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

60 Scopus citations

Abstract

Ganodermic acid S (GAS) [lanosta-7,9(11),24-triene-3β,15α-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-9α,11α-methanoepoxyprostaglandin F(2α)), a thromboxane (TX) A2 mimetic. GAS at 2 μM inhibited 50% of cell aggregation. GAS at 7.5 μM inhibited 80% of Ca2+ mobilization, 40% of phosphorylation of myosin light chain and pleckstrin, 80% of α-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 α(IIb)β3 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-G(q)-phospholipase Cβ1 pathway, but not on the receptor-G(i) pathway. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)587-595
Number of pages9
JournalBiochemical Pharmacology
Volume58
Issue number4
DOIs
StatePublished - 15 08 1999
Externally publishedYes

Keywords

  • Ca mobilization
  • Cyclic AMP
  • Ganodermic acid S
  • Human platelet
  • Thromboxane A

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