Regulation of Endothelin-1 Production by a Thromboxane a2 Mimetic in Rat Heart Smooth Muscle Cells
Document Type
Article
Publication Date
8-21-1996
Description
Thromboxane A2 (TXA2) and ET-1 have been known to play important roles in modulating vascular contraction and growth. The present study was undertaken to examine the effect of TXA2 on the induction of endothelin-1 (ET-1) mRNA and protein levels in smooth muscle cells derived from rat heart. U-46619, a stable TXA2 mimetic, superinduced preproET-1 mRNA in the presence of cycloheximide in these cells. This effect could be blocked by SQ-29548, a TXA2/prostaglandin H2 receptor antagonist and by actinomycin D, an RNA synthesis inhibitor. In addition, H7, a protein kinase C inhibitor, could abolish the induction. Transient transfection experiment revealed that the elevated ET-1 mRNA level after U-46619 treatment was a result of the activation of ET-1 gene activity. The elevated ET-1 message level was accompanied by increased ET-1 release into the cultured medium. These results show that the short-lived TXA2 can induce potent and long-lived ET-1. These findings support a potential role for ET-1 in the pathogenesis of coronary atherosclerosis and hypertension evoked by TXA2.
Citation Information
Chua, Chu Chang; Hamdy, Ronald C.; and Chua, Balvin H.L.. 1996. Regulation of Endothelin-1 Production by a Thromboxane a2 Mimetic in Rat Heart Smooth Muscle Cells. Biochimica et Biophysica Acta - Molecular Cell Research. Vol.1313(1). 1-5. https://doi.org/10.1016/0167-4889(96)00042-0 PMID: 8781542 ISSN: 0167-4889