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Titolo:
LONG-TERM CARBACHOL TREATMENT-INDUCED DOWN-REGULATION OF MUSCARINIC M(2)-RECEPTORS BUT NOT M(2) RECEPTOR MESSENGER-RNA IN A HUMAN LUNG-CELLLINE
Autore:
HADDAD EB; ROUSELL J; MAK JCW; BARNES PJ;
Indirizzi:
NATL HEART & LUNG INST,DEPT THORAC MED,DOVEHOUSE ST LONDON SW3 6LY ENGLAND
Titolo Testata:
British Journal of Pharmacology
fascicolo: 3, volume: 116, anno: 1995,
pagine: 2027 - 2032
SICI:
0007-1188(1995)116:3<2027:LCTDOM>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBELLAR GRANULE CELLS; PROTEIN KINASE-C; CHOLINERGIC RECEPTORS; MESSENGER-RNA; DESENSITIZATION; PHOSPHORYLATION; EXPRESSION; ACTIVATION; AGONISTS; BINDING;
Keywords:
HOMOLOGOUS REGULATION; M(2) MUSCARINIC RECEPTORS; CYCLIC AMP; NORTHERN BLOT; NUCLEAR RNA RUN-ON ASSAY; GENE TRANSCRIPTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
E.B. Haddad et al., "LONG-TERM CARBACHOL TREATMENT-INDUCED DOWN-REGULATION OF MUSCARINIC M(2)-RECEPTORS BUT NOT M(2) RECEPTOR MESSENGER-RNA IN A HUMAN LUNG-CELLLINE", British Journal of Pharmacology, 116(3), 1995, pp. 2027-2032

Abstract

1 The molecular mechanisms involved in the regulation of muscarinic receptor gene expression are poorly understood. We have investigated the effect of homologous stimulation on the regulation of M(2) muscarinic receptor protein and gene in human embryonic lung fibroblasts (HEL 299 cells). 2 Saturation studies performed with the non-selective hydrophilic ([H-3]-N-methyl-scopolamine, [H-3]-NMS) and lipophilic ([H-3]-quinuclidinyl benzilate, [H-3]-QNB) muscarinic antagonists revealed a single class of high affinity binding sites. 3 Carbachol (1 mM) induceda rapid down-regulation of [H-3]-NMS binding sites. Within 12 h, the process had approached steady state with 40 to 60% loss of receptors at 12 and 24 h. 4 The loss of [H-3]-QNB binding sites (40% reduction at24 h) occurred at a slower rate than did loss of [H-3]-NMS binding sites as a result of receptor sequestration. 5 Carbachol treatment was accompanied by a functional desensitization of the receptor after 24 h of agonist treatment. In untreated cells, forskolin induced a large increase in cyclic AMP accumulation which was inhibited significantly bycarbachol. The inhibitory effect of carbachol on forskolin-induced cyclic AMP accumulation was lost following 24 h carbachol stimulation. 6The steady state level of muscarinic m(2) mRNA measured by Northern blot analysis was not affected by carbachol treatment over the time course investigated and half-life studies with actinomycin D suggest thatcarbachol had no effect on the stability of m(2) mRNA. 7 The rate of transcription of m(2) muscarinic receptor gene as measured by nuclear RNA run-on assay was unaltered by carbachol stimulation. 8 These results suggest that homologous sequestration, desensitization, and down-regulation of M(2) muscarinic receptors in HEL 299 cells does not involve transcriptional or post-transcriptional modifications of m(2) muscarinic receptor mRNAs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 06:04:03