title: Expression of the 2',3'-cAMP-adenosine pathway in astrocytes and microglia.
abstract: Many organs express the extracellular 3',5'-cAMP-adenosine pathway (conversion of extracellular 3',5'-cAMP to 5'-AMP and 5'-AMP to adenosine). Some organs release 2',3'-cAMP (isomer of 3',5'-cAMP) and convert extracellular 2',3'-cAMP to 2'- and 3'-AMP and convert these AMPs to adenosine (extracellular 2',3'-cAMP-adenosine pathway). As astrocytes and microglia are important participants in the response to brain injury and adenosine is an endogenous neuroprotectant, we investigated whether these extracellular cAMP-adenosine pathways exist in these cell types. 2',3'-, 3',5'-cAMP, 5'-, 3'-, and 2'-AMP were incubated with mouse primary astrocytes or primary microglia for 1 h and purine metabolites were measured in the medium by mass spectrometry. There was little evidence of a 3',5'-cAMP-adenosine pathway in either astrocytes or microglia. In contrast, both cell types converted 2',3'-cAMP to 2'- and 3'-AMP (with 2'-AMP being the predominant product). Although both cell types converted 2'- and 3'-AMP to adenosine, microglia were five- and sevenfold, respectively, more efficient than astrocytes in this regard. Inhibitor studies indicated that the conversion of 2',3'-cAMP to 2'-AMP was mediated by a different ecto-enzyme than that involved in the metabolism of 2',3'-cAMP to 3'-AMP and that although CD73 mediates the conversion of 5'-AMP to adenosine, an alternative ecto-enzyme metabolizes 2'- or 3'-AMP to adenosine.
authors.affiliation: Departments of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Verrier
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Exo
authors.forename: Travis C
authors.initials: TC
authors.lastname: Jackson
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
authors.forename: Delbert G
authors.initials: DG
authors.lastname: Gillespie
authors.forename: Raghvendra K
authors.initials: RK
authors.lastname: Dubey
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Jackson
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015720:5'-Nucleotidase / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002469:Cell Separation; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014970:Xanthines / Q000494:pharmacology
chemical_list: D000227:Adenine Nucleotides; D010726:Phosphodiesterase Inhibitors; D014970:Xanthines; C010565:2',3'-cyclic AMP; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D000242:Cyclic AMP; D015720:5'-Nucleotidase; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine