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Effects of cAMP‐dependent protein kinase activator and inhibitor on in vivo rolipram binding to phosphodiesterase 4 in conscious rats
Author(s) -
Itoh Tetsuji,
Abe Kohji,
Hong Jinsoo,
Inoue Osamu,
Pike Victor W.,
Innis Robert B.,
Fujita Masahiro
Publication year - 2010
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20728
Subject(s) - rolipram , activator (genetics) , phosphodiesterase , protein kinase a , pde10a , in vivo , chemistry , phosphodiesterase inhibitor , adenosine , phosphodiesterase 3 , second messenger system , medicine , endocrinology , pharmacology , enzyme , biochemistry , biology , receptor , microbiology and biotechnology
Rolipram is a selective inhibitor of phosphodiesterase‐4 (PDE4), and positron emission tomography (PET) using [ 11 C]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 [ 11 C]( R )‐rolipram in comparison to the much less active enantiomer [ 11 C]( 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 [ 11 C]( 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 [ 11 C]( S )‐rolipram binding. These results support the value of measuring in vivo [ 11 C]( R )‐rolipram binding in brain to assess responses to physiological or pharmacological challenges to the cAMP second messenger system. Synapse 64:172–176, 2010. Published 2009 Wiley‐Liss, Inc.