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Titolo:
TRANSFORMING GROWTH-FACTOR-BETA-1 INDUCES TRANSCRIPTIONAL DOWN-REGULATION OF M2 MUSCARINIC RECEPTOR GENE-EXPRESSION
Autore:
HADDAD EB; ROUSELL J; MAK JCW; BARNES PJ;
Indirizzi:
NATL HEART & LUNG INST,DEPT THORAC MED,DOVEHOUSE ST LONDON SW3 6LY ENGLAND NATL HEART & LUNG INST,DEPT THORAC MED LONDON SW3 6LY ENGLAND
Titolo Testata:
Molecular pharmacology
fascicolo: 5, volume: 49, anno: 1996,
pagine: 781 - 787
SICI:
0026-895X(1996)49:5<781:TGITD>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-ADHESION RECEPTORS; FACTOR-BETA; MESSENGER-RNA; TGF-BETA-1 INHIBITION; BINDING; PHOSPHORYLATION; ONCOGENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
E.B. Haddad et al., "TRANSFORMING GROWTH-FACTOR-BETA-1 INDUCES TRANSCRIPTIONAL DOWN-REGULATION OF M2 MUSCARINIC RECEPTOR GENE-EXPRESSION", Molecular pharmacology, 49(5), 1996, pp. 781-787

Abstract

In human embryonic lung fibroblasts, transforming growth factor-beta 1 (TGF-beta 1) induced a time-dependent down-regulation of M(2) muscarinic receptor binding sites as measured with the nonselective hydrophilic ligand [H-3]N-methylscopolamine (NMS). This down-regulation was slow, with 58% loss of all receptors after 24 hr of treatment. The affinity of [H-3]NMS for the remaining sites was unaltered by TGF-beta 1. The loss in [H-3]NMS binding was accompanied by reduced adenylyl cyclase activity and functional desensitization of M(2) muscarinic receptors. Northern blot analyses showed a 72% decrease in the steady state levels of m2 muscarinic receptor mRNA after 24-hr TGF-beta 1 treatment. Recovery of m2 muscarinic receptor mRNA after TGF-beta 1 treatment was slow, with a half-life of similar to 8 hr. There was no effect of TGF-beta 1 on the m2 muscarinic receptor mRNA half-life measured in the presence of actinomycin D, but the rate of m2 muscarinic receptor gene transcription measured with nuclear run-on assay was reduced by 50%, indicating reduced gene transcription. Cycloheximide (10 mu g/ml) pretreatment abolished the TGF-beta 1 effect, indicating that de novo protein synthesis was required for receptor downregulation. In summary, we have shown that TGF-beta 1 induced desensitization and down-regulation of M(2) muscarinic receptor protein and gene that was mediated throughreduction in the rate of m2 receptor gene transcription.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 19:10:01