The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor.
Nat Med
; 7(5): 569-74, 2001 May.
Article
em En
| MEDLINE
| ID: mdl-11329058
ABSTRACT
Angiogenesis has an essential role in many important pathological and physiological settings. It has been shown that vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), a potent cytokine expressed by most malignant tumors, has critical roles in vasculogenesis and both physiological and pathological angiogenesis. We report here that at non-toxic levels, the neurotransmitter dopamine strongly and selectively inhibited the vascular permeabilizing and angiogenic activities of VPF/VEGF. Dopamine acted through D2 dopamine receptors to induce endocytosis of VEGF receptor 2, which is critical for promoting angiogenesis, thereby preventing VPF/VEGF binding, receptor phosphorylation and subsequent signaling steps. The action of dopamine was specific for VPF/VEGF and did not affect other mediators of microvascular permeability or endothelial-cell proliferation or migration. These results reveal a new link between the nervous system and angiogenesis and indicate that dopamine and other D2 receptors, already in clinical use for other purposes, might have value in anti-angiogenesis therapy.
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Base de dados:
MEDLINE
Assunto principal:
Dopamina
/
Fatores de Crescimento Endotelial
/
Linfocinas
/
Isoformas de Proteínas
/
Neovascularização Patológica
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article