Rolipram, a selective inhibitor of phosphodiesterase type 4, pronouncedly enhanced the forskolin-induced promotion of dopamine biosynthesis in primary cultured rat mesencephalic neurons.
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.
Yamashita
N
N
Drug Discovery, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, Japan.
Miyashiro
M
M
Baba
J
J
Sawa
A
A
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000187:drug effects*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004298:Dopamine / Q000096:biosynthesis*; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D008636:Mesencephalon / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011247:Pregnancy; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram; D014748:Vinca Alkaloids / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D014748:Vinca Alkaloids; D015102:3,4-Dihydroxyphenylacetic Acid; D005576:Colforsin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; C013983:vinpocetine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; D004298:Dopamine