Glucocorticosteroids increase beta 2-adrenergic receptor transcription in human lung.
beta 2-Adrenergic receptors (beta 2R) are widely distributed and mediate a wide range of cellular responses in lung. Because glucocorticosteroids increase expression of beta 2R in cell lines, we have investigated the effects of glucocorticoids on the beta 2R mRNA level and the number of beta 2R in human peripheral lung in vitro. Incubation of lung tissues with dexamethasone (Dex) elevated both beta 2R mRNA level (as measured by Northern blot analysis) and beta 2R number (as measured by [125I]iodocyanopindolol binding). The increased accumulation of beta 2R mRNA could be detected at 15 min (1.27 +/- 0.1-fold) and the maximal accumulation occurred at 2 h (2.73 +/- 0.5-fold). The Dex-induced increase in beta 2R mRNA returned to the control level by 17 h. The increase in beta 2R number (1.58 +/- 0.2-fold) was slower, reaching a maximum between 17 and 24 h. Dex increased beta 2R mRNA in a time- and concentration-dependent manner that was abolished by the steroid receptor antagonist mifepristone (RU-38486 or RU-486). The stability of beta 2R mRNA was unchanged by Dex, and a nuclear run-on assay revealed that Dex approximately doubled the transcriptional rate of the beta 2R gene. These observations suggest that glucocorticoids act on steroid receptors to increase beta 2R expression by increasing the rate of beta 2R gene transcription.
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
J C
JC
Mak
M
M
Nishikawa
P J
PJ
Barnes
D000293:Adolescent; D000328:Adult; D003907:Dexamethasone / Q000494:pharmacology*; D004355:Drug Stability; D005260:Female; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D003907:Dexamethasone