title: Adenosine signaling promotes neuronal, catecholaminergic differentiation of primary neural crest cells and CNS-derived CAD cells.
abstract: In neural crest (NC) cultures cAMP signaling is an instructive signal in catecholaminergic, sympathoadrenal cell development. However, the extracellular signals activating the cAMP pathway during NC cell development have not been identified. We demonstrate that in avian NC cultures, evidenced by tyrosine hydroxylase expression and catecholamine biosynthesis, adenosine and not adrenergic signaling, together with BMP2, promotes sympathoadrenal cell development. In NC cultures, addition of the adenosine receptor agonist NECA in the presence of BMP2 promotes sympathoadrenal cell development, whereas the antagonist CGS 15943 or the adenosine degrading enzyme adenosine deaminase (ADA) suppresses TH expression. Importantly, NC cells express A2A and A2B receptors which couple with Gsalpha increasing intracellular cAMP. Employing the CNS-derived catecholaminergic CAD cell line, we also demonstrate that neuronal differentiation mediated by serum withdrawal is further enhanced by treatment with IBMX, a cAMP-elevating agent, or the adenosine receptor agonist NECA, acting via cAMP. By contrast, the adenosine receptor antagonist CGS 15943 or the adenosine degrading enzyme ADA inhibits CAD cell neuronal differentiation mediated by serum withdrawal. These results support that adenosine is a physiological signal in neuronal differentiation of the CNS-derived catecholaminergic CAD cell line and suggest that adenosine signaling is involved in NC cell development in vivo.
authors.affiliation: Department of Basic Medical Sciences, 1246 Lynn Hall, Purdue University, West Lafayette, IN 47907-1246, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Bilodeau
authors.forename: Ming
authors.initials: M
authors.lastname: Ji
authors.forename: Maryline
authors.initials: M
authors.lastname: Paris
authors.forename: Ourania M
authors.initials: OM
authors.lastname: Andrisani
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002395:Catecholamines / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism*; D003370:Coturnix; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D058892:Adenosine Deaminase Inhibitors; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002395:Catecholamines; D016895:Culture Media, Serum-Free; D011799:Quinazolines; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D016212:Transforming Growth Factor beta; D014230:Triazoles; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D000243:Adenosine Deaminase; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine