title: Endothelin-1 enhances β₂-adrenoceptor gene transcription in human lung fibroblasts.
abstract: OBJECTIVE
  The present study aimed to explore possible effects of endothelin-1 (ET-1) on ß(2)-adrenoceptor gene transcription in human lung fibroblasts.
  
  
  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.
  
  
  RESULTS
  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.
authors.affiliation: Institute of Pharmacology & Toxicology University of Bonn, Germany. racke.kurt@uni-bonn.de
authors.forename: Kurt
authors.initials: K
authors.lastname: Racké
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Juergens
authors.forename: Ina
authors.initials: I
authors.lastname: Schütz
authors.forename: Nora
authors.initials: N
authors.lastname: Kämpfer
authors.forename: Margarita
authors.initials: M
authors.lastname: Fuhrmann
authors.forename: Mareille
authors.initials: M
authors.lastname: Warnken
mesh_terms: D048588:Benzoxazines / Q000494:pharmacology; D000077300:Bosentan; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D048588:Benzoxazines; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D018343:Receptors, Adrenergic, beta-2; D013449:Sulfonamides; D003609:Dactinomycin; D003513:Cycloheximide; D000077300:Bosentan; C549647:olodaterol