Endothelin-1 enhances β₂-adrenoceptor gene transcription in human lung fibroblasts.
Copyright policy )Endothelin-1 enhances β₂-adrenoceptor gene transcription in human lung fibroblasts.
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.
- University of Bonn Germany
Sulfonamides, Time Factors, Endothelin-1, Transcription, Genetic, Endothelin A Receptor Antagonists, Bosentan, Fibroblasts, Receptor, Endothelin A, Polymerase Chain Reaction, Receptor, Endothelin B, Benzoxazines, Cell Line, Endothelin B Receptor Antagonists, Up-Regulation, Dactinomycin, Humans, RNA, Messenger, Receptors, Adrenergic, beta-2, Cycloheximide
Sulfonamides, Time Factors, Endothelin-1, Transcription, Genetic, Endothelin A Receptor Antagonists, Bosentan, Fibroblasts, Receptor, Endothelin A, Polymerase Chain Reaction, Receptor, Endothelin B, Benzoxazines, Cell Line, Endothelin B Receptor Antagonists, Up-Regulation, Dactinomycin, Humans, RNA, Messenger, Receptors, Adrenergic, beta-2, Cycloheximide
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