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Titolo:
BOTH ETA AND ETB RECEPTORS ARE INVOLVED IN MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION AND DNA-SYNTHESIS OF ASTROCYTES - STUDY USING ETB RECEPTOR-DEFICIENT RATS (AGANGLIONOSIS RATS)
Autore:
SASAKI Y; HORI S; ODA K; OKADA T; TAKIMOTO M;
Indirizzi:
NOVARTIS PHARMA KK,TAKARAZUKA RES INST TAKARAZUKA HYOGO 6658666 JAPAN CIBA GEIGY JAPAN,INT RES LABS TAKARAZUKA HYOGO 665 JAPAN
Titolo Testata:
European journal of neuroscience
fascicolo: 9, volume: 10, anno: 1998,
pagine: 2984 - 2993
SICI:
0953-816X(1998)10:9<2984:BEAERA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIN RECEPTOR; ADENYLYL CYCLASES; GLIAL-CELLS; COAT COLOR; GENE; CLONING; CDNA; EXPRESSION; CULTURES; BINDING;
Keywords:
G PROTEINS; IRL 1620; IRL 2500; PERTUSSIS TOXIN; SPOTTING LETHAL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
Y. Sasaki et al., "BOTH ETA AND ETB RECEPTORS ARE INVOLVED IN MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION AND DNA-SYNTHESIS OF ASTROCYTES - STUDY USING ETB RECEPTOR-DEFICIENT RATS (AGANGLIONOSIS RATS)", European journal of neuroscience, 10(9), 1998, pp. 2984-2993

Abstract

Endothelin (ET) is known to be a potent mitogen in astrocytes, However, the contribution and signalling pathway of ETA and/or ETB receptor to the proliferation of astrocytes remain unclear. We investigated ET-induced DNA synthesis in astrocytes using ETB receptor-deficient mutant rats (aganglionosis rats: sl/sl). Western blotting with anti-ET receptor subtype-specific antibodies and Scatchard analysis of binding revealed that ETB receptor expression in astrocytes depended on gene dosage (+/+: sl/+: sl/sl = 2:1:0), whereas ETA receptor expression was unchanged among the three genotypes. ET-1 (10 nM) stimulated [H-3]thymidine incorporation and mitogen-activated protein kinase (MAP kinase) activity not only in +/+ via both ETA and ETB receptors, but also in sl/sl astrocytes via ETA receptor with about half the extent of those observed in +/+ astrocytes. Treatment with pertussis toxin (PTX) suppressed the ET-1-induced increases in the incorporation and MAP kinase activity in +/+, but not sl/sl astrocytes, indicating that the ETB receptor-, but not the ETA receptor-, mediated pathway to DNA synthesis involves PTX-sensitive G proteins, e.g. G(i) and/or G(o) (G(i/o)). in +/+ astrocytes, ET-1 (1 nM) stimulated cAMP accumulation, and the ETB receptor-selective agonist IRL 1620 (1 nM) suppressed 10 mu M forskolin-induced cAMP accumulation, suggesting G(s) coupling to the ETA receptor and Oil, coupling to the ETB receptor. On the other hand, ET-1 did not increase cAMP accumulation in sl/sl astrocytes, although ET-1 (1 nM) suppressed the forskolin-induced response, suggesting G(i/o) coupling tothe ETA receptor, Our results suggest the possibility that the selectivity of G protein for ETA receptor is changed from G(s) to G(i/o) in ETB receptor-deficient astrocytes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 00:32:40