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Titolo:
REGULATION OF M2 MUSCARINIC RECEPTOR GENE-EXPRESSION BY PLATELET-DERIVED GROWTH-FACTOR - INVOLVEMENT OF EXTRACELLULAR SIGNAL-REGULATED PROTEIN-KINASES IN THE DOWN-REGULATION PROCESS
Autore:
ROUSELL J; HADDAD EB; LINDSAY MA; BARNES PJ;
Indirizzi:
UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,NATL HEART & LUNG INST,DEPT THORAC MED,DOVEHOUSE ST LONDON SW3 6LY ENGLAND UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,NATL HEART & LUNG INST,DEPT THORAC MED LONDON SW3 6LY ENGLAND
Titolo Testata:
Molecular pharmacology
fascicolo: 6, volume: 52, anno: 1997,
pagine: 966 - 973
SICI:
0026-895X(1997)52:6<966:ROMMRG>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; MAP KINASES; PHOSPHORYLATION; ACTIVATION; INHIBITOR; TYROSINE; MECHANISMS; PATHWAY; POTENT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
J. Rousell et al., "REGULATION OF M2 MUSCARINIC RECEPTOR GENE-EXPRESSION BY PLATELET-DERIVED GROWTH-FACTOR - INVOLVEMENT OF EXTRACELLULAR SIGNAL-REGULATED PROTEIN-KINASES IN THE DOWN-REGULATION PROCESS", Molecular pharmacology, 52(6), 1997, pp. 966-973

Abstract

To study the role of mitogen-activated protein kinase in the regulation of M-2 receptors, we studied the effect of platelet-derived growth factor (PDGF) on M-2 receptor gene expression. PDGF (4 ng/ml) caused atime-dependent decrease in M-2 receptor number and in m2 receptor mRNA levels in HEL 299 cells. The PDGF-induced loss in m2 mRNA required de nova protein synthesis and occurred through a decrease in the rate of transcription of the m2 receptor gene, The down-regulation of M-2 receptors was not accompanied by an uncoupling of the remaining receptors, indicating a large receptor reserve in these cells. Preincubations with the phosphatidylinositol 3-kinase inhibitor wortmannin, the protein kinase C inhibitor GF 109203X and the cAMP-dependent protein kinaseinhibitor H-8 did not attenuate PDGF-induced down-regulation, indicating a lack of involvement of these enzymes in the down-regulation process, Activation of the extracellular signal-regulated protein kinase (ERK) 1 and 2 proteins was measured by an ''in gel'' phosphorylation assay. Carbachol did not activate ERK1 or 2, whereas PDGF and 4 beta-phorbol 13,14-dibutyrate resulted in a large increase in ERK1 and 2 activity along with a decrease in m2 mRNA. Preincubation with PD 098059, aninhibitor of mitogen-activated protein kinase kinase, inhibited PDGF-and 4 beta-phorbol 13,14-dibutyrate-mediated activation of ERK 1 and 2in a concentration-dependent manner. The inhibitory action of PD 098059 was reflected at the mRNA level attenuating both PDGF- and 4 beta-phorbol 13,14-dibutyrate-mediated decreases in m2 mRNA. These results suggest a role of ERK1 and 2 in the regulation of muscarinic m2 receptor gene expression.

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Documento generato il 30/11/20 alle ore 16:37:12