The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor
The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor
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DOI：
10.1038/87895
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发表时间：
2001-05-01
期刊：
影响因子：
82.9
通讯作者：
Mukhopadhyay, D
中科院分区：
文献类型：
--
作者：
Basu, S;Nagy, JA;Mukhopadhyay, D
血管生成在许多重要的病理和生理环境中具有重要作用。血管通透性因子/血管内皮生长因子（VPF/VEGF）是一种由大多数恶性肿瘤表达的强有力的细胞因子，在血管生成以及生理和病理性血管生成中具有重要作用。我们在这里报告说，在无毒水平，神经递质多巴胺强烈和选择性地抑制VPF/VEGF的血管通透性和血管生成活动。多巴胺通过D2多巴胺受体起作用以诱导VEGF受体2的内吞作用，这对于促进血管生成至关重要，从而阻止VPF/VEGF结合、受体磷酸化和随后的信号传导步骤。多巴胺的作用是特异性的VPF/VEGF，并不影响微血管通透性或内皮细胞增殖或迁移的其他介质。这些结果揭示了神经系统和血管生成之间的新联系，并表明多巴胺和其他D2受体，已经在临床上用于其他目的，可能有价值的抗血管生成治疗。
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.