The neurotransmitter dopamine (DA) is an important molecule bridging the nervous and immune systems. DA through autocrine/paracrine manner modulates the functions of immune effector cells by acting through its receptors present in these cells. DA also has unique and opposite effects on T cell functions. Although DA activates naïve or resting T cells, but it inhibits activated T cells. In addition, changes in the expression of DA receptors and their signaling pathways especially in T cells are associated with altered immune functions in disorders like schizophrenia and Parkinson's disease. These results suggest an immunoregulatory role of DA. Therefore targeting DA receptors and their signaling pathways in these cells by using DA receptor agonists and antagonists may be useful for the treatment of diseases where DA induced altered immunity play a pathogenic role.

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Our study shows that dopamine significantly enhances the efficacies of commonly used anticancer drugs and also indicates that an inexpensive drug like dopamine, which is being extensively used in the clinics, might have a role as an antiangiogenic agent for the treatment of breast and colon cancer.

Among the regulators of angiogenesis, catecholamine neurotransmitters are of recent interest because of their opposite roles in the regulation of tumor neovascularization. Norepinephrine and epinephrine by acting through specific adrenoceptors increase the synthesis of proangiogenic factors, and thereby, promote tumor growth. In contrast, dopamine acting via its specific D(2) receptors inhibits tumor growth by suppressing the actions of vascular permeability factor/vascular endothelial growth factor-A on both tumor endothelial and bone marrow-derived endothelial progenitor cells. These reports identify novel endogenous regulators of tumor angiogenesis and also indicate a new and an inexpensive class of antiangiogenic drugs for the treatment of cancer.

Many important physiological and pathological processes are modulated by angiogenesis. It has been shown that initiation of this angiogenic process is an essential early step in the progression of malignant tumors. We report here that ablation of peripheral dopaminergic nerves markedly increased angiogenesis, microvessel density, microvascular permeability, and growth of malignant tumors in mice. Endogenous peripheral dopamine acted through D 2 receptors as significantly more angiogenesis and tumor growth was observed in D 2 dopamine receptor knockout mice in comparison with controls. The vascular endothelial growth factor receptor 2 phosphorylation, which is critical for promoting angiogenesis, was also significantly more in tumor endothelial cells collected from the dopamine-depleted and D 2 dopamine receptor knockout animals. These results reveal that peripheral endogenous neurotransmitter dopamine might be an important physiological regulator of vascular endothelial growth factor-mediated tumor angiogenesis and growth and suggest a novel link between endogenous dopamine, angiogenesis, and tumor growth.