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The brain in vivo expresses the 2′,3′‐cAMP‐adenosine pathway
Author(s) -
Verrier Jonathan D.,
Jackson Travis C.,
Bansal Rashmi,
Kochanek Patrick M.,
Puccio Ava M.,
Okonkwo David O.,
Jackson Edwin K.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07705.x
Subject(s) - adenosine , microdialysis , medicine , endocrinology , phosphodiesterase , inosine , in vivo , phosphodiesterase inhibitor , cyclic nucleotide , adenosine deaminase , biology , chemistry , biochemistry , nucleotide , enzyme , central nervous system , microbiology and biotechnology , gene
J. Neurochem. (2012) 122 , 115–125. Abstract Although multiple biochemical pathways produce adenosine, studies suggest that the 2′,3′‐cAMP‐adenosine pathway (2′,3′‐cAMP→2′‐AMP/3′‐AMP→adenosine) contributes to adenosine production in some cells/tissues/organs. To determine whether the 2′,3′‐cAMP‐adenosine pathway exists in vivo in the brain, we delivered to the brain (gray matter and white matter separately) via the inflow perfusate of a microdialysis probe either 2′,3′‐cAMP, 3′,5′‐cAMP, 2′‐AMP, 3′‐AMP, or 5′‐AMP and measured the recovered metabolites in the microdialysis outflow perfusate with mass spectrometry. In both gray and white matter, 2′,3′‐cAMP increased 2′‐AMP, 3′‐AMP and adenosine, and 3′,5′‐cAMP increased 5′‐AMP and adenosine. In both brain regions, 2′‐AMP, 3‐AMP and 5′‐AMP were converted to adenosine. Microdialysis experiments in 2′,3′‐cyclic nucleotide‐3′‐phosphodiesterase (CNPase) wild‐type mice demonstrated that traumatic brain injury (controlled cortical impact model) activated the brain 2′,3′‐cAMP‐adenosine pathway; similar experiments in CNPase knockout mice indicated that CNPase was involved in the metabolism of endogenous 2′,3′‐cAMP to 2′‐AMP and to adenosine. In CSF from traumatic brain injury patients, 2′,3′‐cAMP was significantly increased in the initial 12 h after injury and strongly correlated with CSF levels of 2′‐AMP, 3′‐AMP, adenosine and inosine. We conclude that in vivo , 2′,3′‐cAMP is converted to 2′‐AMP/3′‐AMP, and these AMPs are metabolized to adenosine. This pathway exists endogenously in both mice and humans.