endothelin-1 and olodaterol

The present study aimed to explore possible effects of endothelin-1 (ET-1) on ß(2)-adrenoceptor gene transcription in human lung fibroblasts.. 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.. 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.. ET-1 can up-regulate β-adrenoceptor gene transcription in human lung fibroblasts.

Topics: Benzoxazines; Bosentan; Cell Line; Cycloheximide; Dactinomycin; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1; Fibroblasts; Humans; Polymerase Chain Reaction; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Adrenergic, beta-2; RNA, Messenger; Sulfonamides; Time Factors; Transcription, Genetic; Up-Regulation