Dopamine and the Inhibition of Angiogenesis Via VEGF

At non-toxic levels, we found that the neurotransmitter dopamine strongly and selectively inhibits the vascular permeabilizing and angiogenic activities of VPF/VEGF. Dopamine acts through D2 dopamine receptors to induce the endocytosis of VEGF receptor 2, critical for promoting angiogenesis, and thereby preventing VPF/VEGF binding, receptor phosphorylation, and subsequent signaling steps. We found the action of dopamine to be 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. Our ongoing studies continue to examine the relationship between dopamine and angiogenesis and the respective proteins involved.