Endothelin-1 enhances beta(2)-adrenoceptor gene transcription in human lung fibroblasts.

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Racke K, Juergens LJ, Schutz I, Kampfer N, Fuhrmann M, Warnken M

Endothelin-1 enhances beta(2)-adrenoceptor gene transcription in human lung fibroblasts.

Life Sci. 2012 Oct 15;91(13-14):540-3. doi: 10.1016/j.lfs.2012.03.025. Epub 2012 Mar 28.

PubMed ID

22483689 [ View in PubMed

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Abstract

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 beta(2)-adrenoceptor mRNA, an effect additive to that of short time (1 hr) exposure to the beta(2)-adrenoceptor agonist olodaterol. The stimulatory effect of ET-1 on beta(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 beta(2)-adrenoceptor gene. ET-1-induced up-regulation of beta(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 beta-adrenoceptor gene transcription in human lung fibroblasts.