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 microM) induced the extension of neurites. A similar result was obtained in 8-Br-cAMP (1 mM)-treated cells. Rolipram, at a low concentration (10 microM) 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 microM) increased the current density (pA/pF) of voltage dependent Ca2+ current (ICa). Both NGF and 8-Br-cAMP also increased the current density of ICa, whereas PMA did not. NGF increased the current density of the nicotinic ACh response whereas rolipram, 8-Br-cAMP and PMA decreased. Rolipram (100 microM), 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.
Akaike
N
N
Department of Neurophysiology Tohoku University School of Medicine, Sendai, Japan.
Furukawa
K
K
Kogure
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004594:Electrophysiology; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D020889:Rolipram; D012701:Serotonin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009414:Nerve Growth Factors; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; D020889:Rolipram; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium