ROLIPRAM ENHANCES THE DEVELOPMENT OF VOLTAGE-DEPENDENT CA2+ CURRENT AND SEROTONIN-INDUCED CURRENT IN RAT PHEOCHROMOCYTOMA CELLS

The effects of chronic treatment (6-8 days) with a phosphodiesterase inhibitor, rolipram, on the expression of voltage-dependent Ca2+ channels, nicotinic acetylcholine (ACh) receptors and 5-hydroxytryptamine (5-HT) receptors were investigated in PC12 cells. The results were compared with the effects of nerve growth factor (NGF), 8-bromo-cyclic AMP (8-Br-cAMP) and phorbol 12-myristate 13-acetate (PMA). In the morphological study rolipram, at a high concentration (100 muM) induced the extension of neurites. A similar result was obtained in 8-Br-cAMP (1 mM)-treated cells. Rolipram, at a low concentration (10 muM) or PMA (10-7 M) did not induce obvious morphological change. NGF (100 ng/ml) induced the extension of long neurites and the formation of neural networks. Rolipram (100 muM) increased the current density (pA/pF) of voltage dependent Ca2+ current (I(Ca)). Both NGF and 8-Br-cAMP also increased the current density of I(Ca), whereas PMA did not. NGF increased the current density of the nicotinic ACh response whereas rolipram, 8-Br-cAMP and PMA decreased. Rolipram (100 muM), NGF (100 ng/ml), and 8-Br-cAMP (1 mM) increased the current density of the 5-HT response whereas the effect of PMA (100 nM) was slight. The results suggest that rolipram is able to contribute to the neuronal development by increasing intracellular cAMP as well as 8-Br-cAMP. Consequently, rolipram behaves like a neurotrophic factor in cultured PC12 cells.