Adrenomedullin stimulates DNA synthesis of rat adrenal zona glomerulosa cells through activation of the mitogen-activated protein kinase-dependent cascade.
J Hypertens
; 19(3 Pt 2): 599-602, 2001 Mar.
Article
em En
| MEDLINE
| ID: mdl-11327635
ABSTRACT
BACKGROUND:
Adrenal zona glomerulosa cells are provided with adrenomedullin receptors. Adrenomedullin has recently been found to enhance proliferation of cultured rat vascular smooth muscle cells and zona glomerulosa cells.OBJECTIVE:
To investigate whether adrenomedullin affects rat zona glomerulosa proliferative activity through the tyrosine kinase and extracellular signal regulated kinases (ERKs) pathways.METHODS:
Dispersed rat zona glomerulosa cells were cultured in vitro for 24 h and then exposed to adrenomedullin (10(-7) mol/l), alone or in the presence of tyrphostin-23 (10(-5) mol/l) or PD-98059 (10(-4) mol/l), for 24 or 48 h. To assess the rate of DNA synthesis, 5-bromo-2'-deoxyuridine (BrdU, 20 mg/ml) was also added to the medium and BrdU-positive cells were detected by immunocytochemistry. The expression of ERKs and the effect of adrenomedullin on ERKs phosphorylation and activity were assayed in dispersed zona glomerulosa cells.RESULTS:
Adrenomedullin significantly increased the percentage of BrdU-positive (phase-S) zona glomerulosa cells; this effect was blocked by either the tyrosine kinase inhibitor, tyrphostin-23, or the mitogen-activated protein kinase kinase (MEK-1) inhibitor, PD-98059. Both zona glomerulosa and zona fasciculata/reticularis express ERK-1 (44 kDa) and ERK-2 (42 kDa) isoforms. However, adrenomedullin phosphorylated ERK-1 and ERK-2 only in the zona glomerulosa; this effect was blunted by the MEK-1 inhibitor, PD98059, and by the calcitonin gene-related peptide type 1 (CGRP-1) receptor antagonist, CGRP8-37, but not by the adrenomedullin C-terminal fragment, ADM22-52.CONCLUSION:
Adrenomedullin stimulates the growth of rat zona glomerulosa cells through activation of CGRP-1 receptor, linked to the tyrosine kinase-MEK-1-ERKs signalling pathway. These results confirm the complex role played by this peptide in the regulation of zona glomerulosa cell physiology.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
DNA
/
Zona Glomerulosa
/
Proteínas Quinases Ativadas por Mitógeno
Limite:
Animals
Idioma:
En
Revista:
J Hypertens
Ano de publicação:
2001
Tipo de documento:
Article