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We have studied how stimulation of protein kinase C and cAMP-dependent protein kinases affect the development of mesencephalic dopaminergic neurons in vitro. IGF-I and bFGF did not activate either second messenger system nor affect the survival of dopaminergic neurons but stimulated dopamine uptake per neuron. Phorbol esters, which stimulate protein kinase C, had no effect on dopamine uptake. Dibutyryl-cAMP caused an increase in dopamine uptake, which was blocked with (Rp)-cAMPS, a specific inhibitor of cAMP-dependent protein kinases. Treating cells with specific phosphodiesterase type IV inhibitors elevated the forskolin-induced increase in dopamine uptake. Furthermore, cAMP, but neither bFGF nor activation dependent astrocyte factor (ADAF), was able to prevent the degeneration of dopaminergic neurons induced by MPP+. These results suggest that increased intracellular cAMP protects dopaminergic neurons in situations of stress and therefore reveal novel possibilities for the treatment of Parkinson's disease.

Type

Journal article

Journal

J Neural Transm Suppl

Publication Date

1995

Volume

46

Pages

217 - 228

Keywords

1-Methyl-4-phenylpyridinium, Animals, Biological Factors, Cell Differentiation, Cell Survival, Cells, Cultured, Cyclic AMP, Dopamine, Fibroblast Growth Factor 2, Insulin-Like Growth Factor I, Neurons, Neuroprotective Agents, Phorbol Esters, Rats, Rats, Sprague-Dawley