Abstract
A selective inhibitor of cyclic nucleotide phosphodiesterase (PDE) 4, rolipram, markedly enhanced the forskolin-induced increase of intracellular dopamine and dihydroxyphenylacetate (DOPAC, a metabolite of dopamine) levels in primary cultured rat mesencephalic neurons and the forskolin-induced increase of dopamine and DOPAC in extracellular medium. Selective inhibitors of PDE2, PDE3, PDE5 and PDE6 did not have such a promoting effect, and the PDE1 inhibitor vinpocetine and W-7 caused dopamine depletion in the neurons. These findings suggested that PDE4 plays a major role in regulating the intracellular cAMP level to control the dopamine biosynthesis in mesencephalic neurons, whereas PDE1 regulates dopamine release instead.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / drug effects*
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3,4-Dihydroxyphenylacetic Acid / metabolism
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4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / pharmacology
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Animals
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Cells, Cultured
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Colforsin / pharmacology*
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Cyclic Nucleotide Phosphodiesterases, Type 1
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Dopamine / biosynthesis*
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Embryo, Mammalian / cytology
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Female
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Mesencephalon / cytology*
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Phosphodiesterase Inhibitors / pharmacology*
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Pregnancy
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Pyrrolidinones / pharmacology*
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Rats
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Rats, Wistar
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Rolipram
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Vinca Alkaloids / pharmacology
Substances
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Phosphodiesterase Inhibitors
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Pyrrolidinones
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Vinca Alkaloids
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3,4-Dihydroxyphenylacetic Acid
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Colforsin
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4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
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vinpocetine
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 1
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Rolipram
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Dopamine