title: Schwann Cells Metabolize Extracellular 2',3'-cAMP to 2'-AMP.
abstract: The 3',5'-cAMP-adenosine pathway (3',5'-cAMP→5'-AMP→adenosine) and the 2',3'-cAMP-adenosine pathway (2',3'-cAMP→2'-AMP/3'-AMP→adenosine) are active in the brain. Oligodendrocytes participate in the brain 2',3'-cAMP-adenosine pathway via their robust expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase; converts 2',3'-cAMP to 2'-AMP). Because Schwann cells also express CNPase, it is conceivable that the 2',3'-cAMP-adenosine pathway exists in the peripheral nervous system. To test this and to compare the 2',3'-cAMP-adenosine pathway to the 3',5'-cAMP-adenosine pathway in Schwann cells, we examined the metabolism of 2',3'-cAMP, 2'-AMP, 3'-AMP, 3',5'-cAMP, and 5'-AMP in primary rat Schwann cells in culture. Addition of 2',3'-cAMP (3, 10, and 30 µM) to Schwann cells increased levels of 2'-AMP in the medium from 0.006 ± 0.002 to 21 ± 2, 70 ± 3, and 187 ± 10 nM/µg protein, respectively; in contrast, Schwann cells had little ability to convert 2',3'-cAMP to 3'-AMP or 3',5'-cAMP to either 3'-AMP or 5'-AMP. Although Schwann cells slightly converted 2',3'-cAMP and 2'-AMP to adenosine, they did so at very modest rates (e.g., 5- and 3-fold, respectively, more slowly compared with our previously reported studies in oligodendrocytes). Using transected myelinated rat sciatic nerves in culture medium, we observed a time-related increase in endogenous intracellular 2',3'-cAMP and extracellular 2'-AMP. These findings indicate that Schwann cells do not have a robust 3',5'-cAMP-adenosine pathway but do have a 2',3'-cAMP-adenosine pathway; however, because the pathway mostly involves 2'-AMP formation rather than 3'-AMP, and because the conversion of 2'-AMP to adenosine is slow, metabolism of 2',3'-cAMP mostly results in the accumulation of 2'-AMP. Accumulation of 2'-AMP in peripheral nerves postinjury could have pathophysiological consequences.
authors.affiliation: Department of Pharmacology and Chemical Biology (J.D.V., E.K.J.), Department of Critical Care Medicine (P.M.K.), and Safar Center for Resuscitation Research (P.M.K.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Verrier
authors.affiliation: Department of Pharmacology and Chemical Biology (J.D.V., E.K.J.), Department of Critical Care Medicine (P.M.K.), and Safar Center for Resuscitation Research (P.M.K.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.affiliation: Department of Pharmacology and Chemical Biology (J.D.V., E.K.J.), Department of Critical Care Medicine (P.M.K.), and Safar Center for Resuscitation Research (P.M.K.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania edj@pitt.edu.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Jackson
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D045604:Extracellular Fluid / Q000378:metabolism*; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism*
chemical_list: D000227:Adenine Nucleotides; D000249:Adenosine Monophosphate; C010565:2',3'-cyclic AMP