Endothelin-1 and platelet activating factor stimulate thromboxane A2 biosynthesis in rat vascular smooth muscle cells.
The effect of endothelin-1 (ET-1) on the release of thromboxane A2 (TXA2) was examined in cultured rat vascular smooth muscle cells (VSMC). ET-1 (10(-11) to 10(-6) M) significantly stimulated the release of thromboxane B2 (TXB2), a stable metabolite of TXA2. These effects of ET-1 were blocked by a cyclooxygenase inhibitor (indomethacin), a TXA2 synthetase inhibitor (CV-1451) and a specific platelet activating factor (PAF) antagonist (CV-6209). Additionally, PAF (10(-11) to 10(-6) M) stimulated the TXB2 release. Pretreatment with the phospholipase A2 inhibitor dexamethasone potently inhibited both ET-1 and PAF-induced elevation of cytosolic free Ca2+ concentrations [( Ca2+]i) in fura-2-loaded VSMC. These results clearly demonstrate that both ET-1 and PAF stimulate TXA2 biosynthesis in cultured rat VSMC, and TXA2 may contribute to the elevation of [Ca2+]i induced by ET-1 or PAF in VSMC. Furthermore, the stimulation of TXA2 biosynthesis may be a result of PLA2 activation by not only ET-1 but also PAF.
Takayasu-Okishio
M
M
Research and Development Division, Takeda Chemical Industries Ltd, Osaka, Japan.
Terashita
Z
Z
Kondo
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis
D016232:Endothelins; D010972:Platelet Activating Factor; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium