Inhibition by diallyl trisulfide, a garlic component, of intracellular Ca(2+) mobilization without affecting inositol-1,4, 5-trisphosphate (IP(3)) formation in activated platelets.
Garlic has been used in herbal medicine for thousands of years. Some reports have shown that garlic has protective effects against atherosclerosis and inhibits platelet function. In this study, we investigated the mechanism by which diallyl trisulfide (DT), a component of garlic, inhibits platelet function. DT inhibited platelet aggregation and Ca(2+) mobilization in a concentration-dependent manner without increasing intracellular cyclic AMP and cyclic GMP. DT also had no inhibitory effects on thromboxane A(2) (TXA(2)) production in cell-free systems. Collagen-related peptide (CRP)-induced Ca(2+) mobilization is regulated by phospholipase C-gamma2 (PLC-gamma2) activation. We evaluated the effect of DT on tyrosine phosphorylation of PLC-gamma2 and the production of inositol-1,4,5-trisphosphate (IP(3)). DT at concentrations that inhibited platelet aggregation and Ca(2+) mobilization had no effects on tyrosine phosphorylation of PLC-gamma2 or on the formation of IP(3) induced by CRP. Similar results were obtained with thrombin-induced platelet activation. DT inhibited platelet aggregation and Ca(2+) mobilization induced by thrombin without affecting the production of IP(3.) We then evaluated the effect of DT on the binding of IP(3) to its receptor. DT at high concentrations partially blocked the binding of IP(3) to its receptor. Taken together, our findings suggest that the agent suppresses Ca(2+) mobilization at a step distal to IP(3) formation. DT may provide a good tool for investigating Ca(2+) mobilization.
Qi
R
R
Department of Clinical and Laboratory Medicine, Yamanashi Medical University, Yamanashi, Japan.
Liao
F
F
Inoue
K
K
Yatomi
Y
Y
Sato
K
K
Ozaki
Y
Y
D000498:Allyl Compounds / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005737:Garlic / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D010446:Peptide Fragments / Q000502:physiology; D051966:Phospholipase C gamma; D010766:Phosphorylation; D010946:Plants, Medicinal; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013440:Sulfides / Q000494:pharmacology*; D013917:Thrombin / Q000502:physiology; D013928:Thromboxane A2 / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D000498:Allyl Compounds; D007527:Isoenzymes; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D013440:Sulfides; C042577:diallyl trisulfide; D014443:Tyrosine; D013928:Thromboxane A2; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D013917:Thrombin; D006152:Cyclic GMP; D002118:Calcium