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Titolo:
TRANSCRIPTIONAL DOWN-REGULATION OF M2 MUSCARINIC RECEPTOR GENE-EXPRESSION IN HUMAN EMBRYONIC LUNG (HEL-299) CELLS BY PROTEIN-KINASE-C
Autore:
ROUSELL J; HADDAD EB; 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:
The Journal of biological chemistry
fascicolo: 13, volume: 270, anno: 1995,
pagine: 7213 - 7218
SICI:
0021-9258(1995)270:13<7213:TDOMMR>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
MESSENGER-RNA EXPRESSION; ACETYLCHOLINE-RECEPTOR; DIFFERENTIAL REGULATION; BINDING-PROPERTIES; ADENYLYL CYCLASE; AGONIST EXPOSURE; PHORBOL ESTERS; PHOSPHORYLATION; ACTIVATION; M1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
J. Rousell et al., "TRANSCRIPTIONAL DOWN-REGULATION OF M2 MUSCARINIC RECEPTOR GENE-EXPRESSION IN HUMAN EMBRYONIC LUNG (HEL-299) CELLS BY PROTEIN-KINASE-C", The Journal of biological chemistry, 270(13), 1995, pp. 7213-7218

Abstract

m2 muscarinic receptor gene expression was investigated following stimulation of protein kinase C (PKC) with the phorbol ester 4 beta-phorbol dibutyrate (PDBu) in HEL 299 cells. PDBu (100 nM) caused a time dependent decrease in the steady-state levels of m2 receptor mRNA and in specific [H-3]N-methyl scopolamine binding. Preincubation with the PKCinhibitor GF-109203X inhibited the reduction in M(2) receptor and mRNA levels induced by PDBu, confirming the involvement of PKC, Chronic PDBu treatment also caused desensitization of the receptor as forskolin-stimulated cAMP accumulation, inhibited by carbachol in control cells, was lost upon treatment with PDBu for 24 h. Co-incubation with PDBu and the protein synthesis inhibitor cycloheximide, inhibited PDBu-mediated reduction of m2 receptor mRNA, indicating new protein synthesis is required for down-regulation. Half-life studies using the transcriptional inhibitor actinomycin D suggested that the stability of the m2 receptor mRNA was not altered by PDBu treatment (t(1/2) = 2 h) Nuclear run on assays showed a 50% reduction in the rate of m2 receptor gene transcription after treatment with PDBu for 12 h. In conclusion we haveprovided evidence for heterologous regulation of m2 receptor gene expression through changes in gene transcription resulting in uncoupling of M(2) receptors. Furthermore, the synthesis of an unidentified factor is required for the down-regulation process.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 00:59:11