Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
BETA-ADRENOCEPTOR-MEDIATED DOWN-REGULATION OF M(2) MUSCARINIC RECEPTORS - ROLE OF CYCLIC ADENOSINE 5'-MONOPHOSPHATE-DEPENDENT PROTEIN-KINASE AND PROTEIN-KINASE-C
Autore:
ROUSELL J; HADDAD EB; MAK JCW; WEBB BLJ; GIEMBYCZ MA; 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: 4, volume: 49, anno: 1996,
pagine: 629 - 635
SICI:
0026-895X(1996)49:4<629:BDOMMR>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEURO-BLASTOMA CELLS; CHOLINERGIC RECEPTORS; SMOOTH-MUSCLE; ACTIVATION; AGONISTS; CALCIUM; RELEASE; POTENT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
J. Rousell et al., "BETA-ADRENOCEPTOR-MEDIATED DOWN-REGULATION OF M(2) MUSCARINIC RECEPTORS - ROLE OF CYCLIC ADENOSINE 5'-MONOPHOSPHATE-DEPENDENT PROTEIN-KINASE AND PROTEIN-KINASE-C", Molecular pharmacology, 49(4), 1996, pp. 629-635

Abstract

Stimulation of beta(2)-adrenoceptors with the selective beta(2) agonist procaterol caused a biphasic decrease in cell surface M(2) muscarinic receptor number in human embryonic lung 299 cells when measured with the hydrophilic antagonist [H-3]N-methylscopolamine. In contrast, total muscarinic receptor number, measured with the lipophilic antagonist [H-3]quinuclidinylbenzilate, decreased after only 24-hr treatments with procaterol. The loss in receptor number at 24 hr was mimicked withthe use of forskolin and the cAMP analogue 8-bromo-cAMP, indicating acAMP-mediated mechanism. Northern blot analysis showed a small and transient increase in m2-receptor mRNA levels up to 2 hr but no long term (24 hr) effect. Chronic (24-hr) treatment with 8-bromo-cAMP also hadno effect on m2 muscarinic receptor mRNA, whereas forskolin caused a 50% reduction in the steady state levels of m2 mRNA that could be onlypartially blocked by the cAMP-dependent protein kinase inhibitor H-8 and the protein kinase C inhibitor GF 109203X. Procaterol-induced down-regulation of M(2) receptors was fully blocked by [2-(methylamino)ethyl]-5'-isoquinoline-sulfonamide and (3-dimethylaminopropyl)-inol-3-yl]-3-(indole-3-yl) maleimide, implicating both of these kinases in the M(2) muscarinic receptor down-regulation. Conversely, the forskolin- and 8-bromo-cAMP-induced down-regulation was only partially inhibited and unaffected by these inhibitors, respectively. In control cells and those treated with procaterol for less than or equal to 2 hr, cAMP generation was significantly inhibited by carbachol. The inhibitory effectof carbachol was, however, lost after 24-hr exposure to procaterol. This desensitization was partially reversed by preincubations with H-8 and GF 109203X. Collectively, these results suggest that transregulation of M(2) muscarinic receptors by beta(2)-adrenoceptor stimulation can be demonstrated at the protein level in human embryonic lung 299 cells. Furthermore, a role is suggested for cAMP-dependent kinase and PKCin M(2) muscarinic receptor down-regulation and their functional desensitization.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 08:17:47