| Autor: |
Mak, Judith C.W., Rousell, Jonathan, Haddad, El-Bdaoui, Barnes, Peter J. |
| Předmět: |
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| Zdroj: |
Naunyn-Schmiedeberg's Archives of Pharmacology; Dec2000, Vol. 362 Issue 6, p520-525, 6p |
| Abstrakt: |
Transforming growth factor-β1 (TGF-β1) has been shown to modulate β-adrenoceptor number and function in cultured human tracheal smooth muscle cells and cardiac fibroblasts, but the mechanism is unclear. In this study, we have characterized the β2-adrenoceptor expression by radioligand binding assay, Northern blot analysis and measurement of intracellular cAMP accumulation in a human embryonic lung fibroblast cell line (HEL299 cells). Treatment with TGF-β1 caused a time-dependent decrease in β2-adrenoceptor mRNA, and in receptor number after 24 h. Furthermore, nuclear run-on assays showed a 35% reduction in the transcription rate of the β2-adrenoceptor gene with no alteration in stability of the β2-adrenoceptor mRNA. After TGF-β1 treatment, the basal, procaterol- and forskolin-stimulated cAMP accumulations were also decreased. Cycloheximide inhibited TGF-β1-mediated reduction of β2-adrenoceptor mRNA and protein, whilst alone caused induction of β2-adrenoceptor mRNA without any effect on receptor number. In summary, TGF-β1 induces β2-adrenoceptor desensitization through the alteration in adenylyl cyclase activity and down-regulation of β2-adrenoceptor mRNA and protein through the reduction in the rate of β2-adrenoceptor gene transcription. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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