Dopamine (DA)3 is one of the major neurotransmitters in the brain. In the central nervous system, it regulates various important functions like emotions, motivations, feelings of pleasure, addiction, and movement (1, 2). In the periphery, it regulates blood pressure, heart rate, gut motility, endocrine, and kidney functions (3-5). Recent reports indicate that DA influences different functions of the immune effector cells, most importantly normal T lymphocytes (6 -11). T lymphocytes can synthesize, transport, and reuptake DA (12, 13). DA, in turn, modulates the functions of these immune effector cells by acting through its specific classes of receptors expressed in these cells.The Our previous reports indicate that in activated normal human T cells, stimulation of D 1 DA receptors inhibit cell proliferation by elevating intracellular cAMP (24). Similarly, stimulation of D 2 receptors in T cells has been shown to inhibit activated T cell receptor (TCR)-induced cell proliferation and secretion of IL-2, . Also, DA D 4 receptors have a pivotal role in maintaining T cell quiescence (26). All of these reports indicate that other than being an important regulator of immunity (10, 11), DA also plays a key role in the regulation of normal human T cell functions (27,28).Therefore, it is interesting to find out the expression profile of DA receptors and their regulatory role, if any, in pathologically abnormal T cells with respect to their uncontrolled proliferation. Accordingly, to examine the role of dopaminergic regulation in abnormally proliferating T cells, acute T lymphoblastic leukemic cells (Jurkat) were selected (29). EXPERIMENTAL PROCEDURESCell Line-The acute lymphoblastic leukemia T cell line (Jurkat cells) was obtained from the American Type Culture Collection. The cells were grown in RPMI 1640 medium with 1.5 mM L-glutamine, Earle's salt, and sodium bicarbonate and supplemented with 10% fetal bovine serum (29).

Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA) is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D2 DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D2 DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D2 DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D2 DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities.

The overexpression of insulin-like growth factor receptor-I (IGF-IR) and the activation of its signaling pathways both play critical roles in the development and progression of gastric cancer. Dopamine (DA), a major enteric neurotransmitter, has been reported to have a wide variety of physiological functions in the gastrointestinal tract, including the stomach. We have previously reported that both DA and tyrosine hydroxylase, the rate-limiting enzyme required for the synthesis of DA, are lost in malignant gastric tissues.