D1 and D2 Dopamine Receptor-mediated Inhibition of Activated Normal T Cell Proliferation Is Lost in Jurkat T Leukemic Cells

Abstract

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).

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