Rolipram, a Selective Inhibitor of Phosphodiesterase Type 4, Pronouncedly Enhanced the Forskolin-Induced Promotion of Dopamine Biosynthesis in Primary Cultured Rat Mesencephalic Neurons
Nobuyuki Yamashita, Mio Miyashiro, Jun Baba and Aiko Sawa (*)
Drug Discovery, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222, Japan
(*) To whom correspondence should be addressed.
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.
Keywords: Phosphodiesterase, Rolipram, Dopamine biosynthesis