Abstract
Aim:
To investigate the effects of tanshinone IIA (Tan IIA) on the regulation of the production of endothelin (ET)-1 (including large ET-1), mRNA levels of ET-1, endothelin-converting enzyme-1 (ECE-1), endothelin-A receptor (ETA) and endothelin-B receptor (ETB) induced by TNF-α in rat brain microvascular endothelial cells (BMVEC).
Methods:
The ET-1 release (including large ET-1) into the culture medium was determined by enzyme immunoassay. The levels of ET-1, ECE-1, ETA, and ETB mRNA were measured by RT-PCR. Endothelin receptor binding was also tested.
Results:
The induction of ET-1 release by TNF-α from cultured BMVEC was dose-dependently reduced by Tan IIA, but large ET-1 levels progressively increased in response to Tan IIA; the mRNA expression of ET-1 was unaffected. Tan IIA also caused a decrease in ETA receptor mRNA and ECE-1 expression in a dose-dependent manner. Endothelin receptor binding was unaltered in BMVEC stimulated with TNF-α alone or a combination of TNF-α and Tan IIA.
Conclusion:
These findings suggest that Tan IIA may inhibit ET-1 production in TNF-α-induced BMVEC through the suppression of ECE-1 synthesis.
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Tang, C., Wu, Ah., Xue, Hl. et al. Tanshinone IIA inhibits endothelin-1 production in TNF-α-induced brain microvascular endothelial cells through suppression of endothelin-converting enzyme-1 synthesis. Acta Pharmacol Sin 28, 1116–1122 (2007). https://doi.org/10.1111/j.1745-7254.2007.00598.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00598.x
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