5-hydroxytryptamine stimulates phosphorylation of p44/p42 mitogen-activated protein kinase activation in bovine aortic endothelial cell cultures.
J Cardiovasc Pharmacol
; 35(3): 398-402, 2000 Mar.
Article
en En
| MEDLINE
| ID: mdl-10710124
ABSTRACT
5-Hydroxytryptamine (5-HT) is sequestered and released by endothelial cells, acts as an endothelial cell mitogen, promotes the release of nitric oxide (NO), and has been associated with the p44/p42 mitogen-activated protein kinase (MAPK) cascade. NO also acts as a cell mitogen and promotes signals that culminate in the phosphorylation of MAPK. The aim of this study was to test whether endothelial 5-HT receptors stimulate dual (tyrosyl- and threonyl-) phosphorylation of MAPK through a mitogen-activated protein kinase kinase-1 (MEK-1) and eNOS-dependent pathway in bovine aortic endothelial cells (BAECs). As shown by Western blot analysis, 5-HT and the 5-HT1B-selective agonist 5-nonyloxytryptamine (5-NOT) stimulate time- and concentration-dependent (0.001-10 microM) phosphorylation of MAPK in these cells. The agonist-stimulated phosphorylation of MAPK was blocked by the 5-HT1b-receptor antagonist isamoltane (0.01-10 p3M) and the MEK-1 inhibitor PD 098059 ([2-(2'-amino-3'-methoxy-phenyl)-oxanaphthalen-4-one]; 0.01-10 microM¿. The eNOS inhibitor L-N(omega)-iminoethyl-L-ornithine (L-NIO; 0.01-10 microM) failed to block the 1 microM 5-NOT-stimulated responses. Our findings suggest that the 5-HT receptors (specifically 5-HT1B) mediate signals to MEK-1 and subsequently to MAPK through an eNOS-independent pathway in BAECs.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ornitina
/
Flavonoides
/
Endotelio Vascular
/
Serotonina
/
Proteína Quinasa 1 Activada por Mitógenos
/
Inhibidores Enzimáticos
/
Músculo Liso Vascular
Límite:
Animals
Idioma:
En
Revista:
J Cardiovasc Pharmacol
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos