Endothelin-1 enhances ß2-adrenoceptor gene transcription in human lung fibroblasts.

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