title: Adenosine A₂a receptors and O₂ sensing in development.
abstract: Reduced mitochondrial oxidative phosphorylation, via activation of adenylate kinase and the resulting exponential rise in the cellular AMP/ATP ratio, appears to be a critical factor underlying O₂ sensing in many chemoreceptive tissues in mammals. The elevated AMP/ATP ratio, in turn, activates key enzymes that are involved in physiologic adjustments that tend to balance ATP supply and demand. An example is the conversion of AMP to adenosine via 5'-nucleotidase and the resulting activation of adenosine A(₂A) receptors, which are involved in acute oxygen sensing by both carotid bodies and the brain. In fetal sheep, A(₂A) receptors associated with carotid bodies trigger hypoxic cardiovascular chemoreflexes, while central A(₂A) receptors mediate hypoxic inhibition of breathing and rapid eye movements. A(₂A) receptors are also involved in hypoxic regulation of fetal endocrine systems, metabolism, and vascular tone. In developing lambs, A(₂A) receptors play virtually no role in O₂ sensing by the carotid bodies, but brain A(₂A) receptors remain critically involved in the roll-off ventilatory response to hypoxia. In adult mammals, A(₂A) receptors have been implicated in O₂ sensing by carotid glomus cells, while central A(₂A) receptors likely blunt hypoxic hyperventilation. In conclusion, A(₂A) receptors are crucially involved in the transduction mechanisms of O₂ sensing in fetal carotid bodies and brains. Postnatally, central A(₂A) receptors remain key mediators of hypoxic respiratory depression, but they are less critical for O₂ sensing in carotid chemoreceptors, particularly in developing lambs.
authors.affiliation: Department of Obstetrics and Gynecology; Brain Research Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA. bkoos@mednet.ucla.edu
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Koos
mesh_terms: D000222:Adaptation, Physiological; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002344:Carotid Body / Q000254:growth & development / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000378:metabolism*; D004734:Energy Metabolism; D005133:Eye Movements; D006706:Homeostasis; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism*; D012123:Pulmonary Ventilation; D043683:Receptors, Adenosine A2 / Q000378:metabolism*; D012018:Reflex; D015398:Signal Transduction
chemical_list: D043683:Receptors, Adenosine A2; D000241:Adenosine; D010100:Oxygen