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

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)172-176
Number of pages5
JournalSynapse
Volume64
Issue number2
DOIs
Publication statusPublished - Feb 2010

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Effects of cAMP-dependent protein kinase activator and inhibitor on in vivo rolipram binding to phosphodiesterase 4 in conscious rats'. Together they form a unique fingerprint.

Cite this