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Endothelin-1 enhances β₂-adrenoceptor gene transcription in human lung fibroblasts
Kurt Racké1, Lisa J Juergens, Ina Schütz
1Institute of Pharmacology & Toxicology University of Bonn, Germany. racke.kurt@uni-bonn.de
Aims:
The present study aimed to explore possible effects of endothelin-1 (ET-1) on ß(2)-adrenoceptor gene transcription in human lung fibroblasts.
Main Methods:
MRC-5 human lung fibroblasts were cultured in absence or presence of test substances, followed by ß(2)-adrenoceptor mRNA determination by quantitative real time PCR.
Key Findings:
ET-1 caused a marked and rapid in onset (1 hr) increase in β(2)-adrenoceptor mRNA, an effect additive to that of short time (1 hr) exposure to the β(2)-adrenoceptor agonist olodaterol. The stimulatory effect of ET-1 on β(2)-adrenoceptor mRNA was prevented by the non-selective ET-A/ET-B receptor antagonist bosentan, indicating that it was mediated via specific ET receptors. In the presence of actinomycin D the effect of ET-1 was prevented indicating that ET-1 acts via increased transcription of the β(2)-adrenoceptor gene. ET-1-induced up-regulation of β(2)-adrenoceptor mRNA was also seen in the presence of cycloheximide excluding indirect effects via up-regulation of other regulatory proteins.
Conclusions:
ET-1 can up-regulate β-adrenoceptor gene transcription in human lung fibroblasts.
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