Effects of cAMP-dependent protein kinase activator and inhibitor on in vivo rolipram binding to phosphodiesterase 4 in conscious rats

Tetsuji Itoh, Kohji Abe, Jinsoo Hong, Osamu Inoue, Victor W. Pike, Robert B. Innis, Masahiro Fujita

研究成果査読

16 被引用数 (Scopus)

抄録

Rolipram is a selective inhibitor of phosphodiesterase-4 (PDE4), and positron emission tomography (PET) using [11C]rolipram can monitor the in vivo activity of this enzyme that is part of the cAMP second messenger cascade. cAMP-dependent protein kinase (PKA) phosphorylates PDE4 and increases both enzyme activity and affinity for rolipram. In the present PET study, we examined effects of PKA modulators in conscious rats on the binding of [ 11C](R)-rolipram in comparison to the much less active enantiomer [11C](S)-rolipram. Unilateral injection of a PKA activator (dibutyryl-cAMP) and a PKA inhibitor (Rp-adenosine-3′,5′-cyclic monophosphorothioate) into the striatum significantly increased and decreased, respectively, the binding of [11C](R)-rolipram. These effects were not caused by changes in blood flow or delivery of radioligand to brain, since these agents had no effect on the binding of [11C](S)-rolipram binding. These results support the value of measuring in vivo [ 11C](R)-rolipram binding in brain to assess responses to physiological or pharmacological challenges to the cAMP second messenger system.

本文言語English
ページ(範囲)172-176
ページ数5
ジャーナルSynapse
64
2
DOI
出版ステータスPublished - 2月 2010
外部発表はい

ASJC Scopus subject areas

  • 細胞および分子神経科学

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