Author(s): TakayasuOkishio M, Terashita Z, Kondo K, TakayasuOkishio M, Terashita Z, Kondo K
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Abstract 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.
This article was published in Biochem Pharmacol
and referenced in Journal of AIDS & Clinical Research