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The brain in vivo expresses the 2',3'-cAMP-adenosine pathway.

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.
AuthorsJonathan D Verrier, Travis C Jackson, Rashmi Bansal, Patrick M Kochanek, Ava M Puccio, David O Okonkwo, Edwin K Jackson
JournalJournal of neurochemistry (J Neurochem) Vol. 122 Issue 1 Pg. 115-25 (Jul 2012) ISSN: 1471-4159 [Electronic] England
PMID22360621 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.
Chemical References
  • Adenine Nucleotides
  • Adenosine Monophosphate
  • 2',3'-cyclic AMP
  • Cyclic AMP
  • 2',3'-Cyclic-Nucleotide Phosphodiesterases
  • Adenosine
Topics
  • 2',3'-Cyclic-Nucleotide Phosphodiesterases (deficiency)
  • Adenine Nucleotides (metabolism)
  • Adenosine (metabolism)
  • Adenosine Monophosphate (metabolism)
  • Adult
  • Animals
  • Brain (cytology, metabolism)
  • Brain Injuries (cerebrospinal fluid, pathology)
  • Cyclic AMP (metabolism)
  • Disease Models, Animal
  • Extracellular Fluid (metabolism)
  • Female
  • Gene Expression Regulation (genetics)
  • Glasgow Coma Scale
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microdialysis
  • Signal Transduction (genetics, physiology)
  • Young Adult

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