Glucocorticoids down-regulate β1-adrenergic-receptor expression by suppressing transcription of the receptor gene

J. Kiely, J. R. Hadcock, Suleiman Bahouth, C. C. Malbon

Research output: Contribution to journalArticle

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Abstract

The expression of β2-adrenergic receptors is up-regulated by glucocorticoids. In contrast β1-adrenergic receptors display glucocorticoid-induced down-regulation. In rat C6 glioma cells, which express both of these subtypes of β-adrenergic receptors, the synthetic glucocorticoid dexamethasone stimulates no change in the total β-adrenergic receptor content, but rather shifts the β12 ratio from 80:20 to 50:50. Radioligand binding and immunoblotting demonstrate a sharp decline in β1-adrenergic receptor expression. Metabolic labelling of cells with [35S]-methionine in tandem with immunoprecipitation by β1-adrenergic-receptor-specific antibodies reveals a sharp decline in the synthesis of the receptor within 48 h for cells challenged with glucocorticoid. Steady-state levels of β1-adrenergic-receptor mRNA declined from 0.47 to 0.26 amol/μg of total cellular RNA within β12 h of dexamethasone challenge, as measured by DNA-excess solution hybridization. The stability of receptor mRNA was not influenced by glucocorticoid; the half-lives of the β1- and β2-subtype mRNAs were 1.7 and 1.5 h respectively. Nuclear run-on assays revealed the basis for the down-regulation of receptor expression, i.e. a sharp decline in the relative rate of transcription for the β1-adrenergic-receptor gene in nuclei from dexamethasone-treated as compared with vehicle-treated cells. These data demonstrate transcriptional suppression as a molecular explanation for glucocorticoid-induced down-regulation of β1-adrenergic receptors.

Original languageEnglish (US)
Pages (from-to)397-403
Number of pages7
JournalBiochemical Journal
Volume302
Issue number2
DOIs
StatePublished - Jan 1 1994

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Transcription
Adrenergic Receptors
Glucocorticoids
Down-Regulation
Genes
Dexamethasone
Messenger RNA
RNA Stability
Immunoprecipitation
Immunoblotting
Glioma
Methionine
Labeling
Rats
Assays
Cells
RNA
Antibodies
DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Glucocorticoids down-regulate β1-adrenergic-receptor expression by suppressing transcription of the receptor gene. / Kiely, J.; Hadcock, J. R.; Bahouth, Suleiman; Malbon, C. C.

In: Biochemical Journal, Vol. 302, No. 2, 01.01.1994, p. 397-403.

Research output: Contribution to journalArticle

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