Role Of Dopamine D2 Receptor During Pituitary Tumor Cell Apoptosis

In attempt to understand the role of the dopamine D2 receptor in signaling pathway involved in cell death in pituitary tumor cells, we have generated recombinant cell line, which express two isoforms of dopamine D2 receptor, D2L (Long) and D2S (Short). Bromocriptine induced a potent decrease of cell viability in GH3, GH3D2L and GH3D2S cells, whereas, treatment of dopamine or quinpirole decrease significantly in cell numbers only in GH3D2L and GH3D2S cells. Treatment of haloperidol rescued the dopamine- or partial bromocriptine- induced decrease of cell viability in GH3D2L and GH3D2S cells but not the effect of bromocriptine in GH3 cell. Treatment with dopamine and low dose bromocriptine resulted in cell death accompanied with the DNA laddering and activation of caspase-3 only in GH3D2L and GH3D2S cells, which were blunted by haloperidol, showing that dopamine-induced cell death in these cells is mediated by dopamine D2 receptors. Furthermore, dopamine receptor stimulation induced generation ofreactive oxygen species (ROS) and the cell death induced by dopamine was blocked by the antioxidant, N-acetylcysteine (NAC). These data suggest that the dopamine induces apoptosis via dopamine D2 receptors involving oxidative stress and that bromocriptine utilize differential pathway to execute cell death using either D2 receptor- dependent and -independent pathways in pituitary tumor cells.