The effect of dopamine on the growth, phenotypes (morphological and biochemical) and programmed cell death (apoptosis) of the human neuronal NMB cell line was examined. Exposure to 20–50 µM of dopamine decreased cell growth, induced an apparent differentiated cell morphology and increased 3H-dopamine uptake. At higher concentrations (100–300 µM) dopamine was neurotoxic and induced apoptosis, as reported previously. The observed effects of both low and high doses of dopamine were blocked by cocaine, which suggested involvement of dopamine transporters. Indeed, several experiments demonstrated the relationship between dopamine uptake of cells and their vulnerability to the toxic effect of dopamine. High concentrations of dopamine, which induced apoptosis, also increased p53 levels, detected by RT-PCR analysis and immunoblotting, whereas lower dopamine concentrations, which induced a differentiated phenotype, did not increase p53 immunoblotting. Dibutyryl-cAMP and dimethyl sulfoxide, which induced differentiation but not apoptosis of the NMB cells, did not increase p53 expression. These findings provide an insight into the role of dopamine, dopamine transporters and p53 in the differentiation and apoptosis of dopaminergic neurons, which will further our understanding of neuronal development and neurodegenerative diseases.

Keywords:
Neurodegeneration, Parkinson’s disease, Programmed cell death, DNA damage, Aging, Catecholamine
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© 2002 S. Karger AG, Basel
2002
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