Department of Obstetrics and Gynecology; Brain Research Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R601-22. doi: 10.1152/ajpregu.00664.2010. Epub 2011 Jun 15.
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.
通过激活腺嘌呤激酶，导致细胞 AMP/ATP 比值呈指数上升，从而减少线粒体氧化磷酸化，似乎是哺乳动物许多化学感受组织中 O₂ 感应的关键因素。反过来，升高的 AMP/ATP 比值又会激活参与生理调节的关键酶，这些调节有助于平衡 ATP 的供应和需求。一个例子是 AMP 通过 5'-核苷酸酶转化为腺苷，并激活参与颈动脉体和大脑急性氧感应的腺苷 A₂A 受体。在胎羊中，与颈动脉体相关的 A₂A 受体触发低氧心血管化学反射，而中枢 A₂A 受体介导低氧抑制呼吸和快速眼球运动。A₂A 受体还参与低氧调节胎儿内分泌系统、代谢和血管张力。在发育中的羔羊中，A₂A 受体在颈动脉体的 O₂ 感应中几乎不起作用，但脑 A₂A 受体在低氧通气反应的衰减中仍然起着至关重要的作用。在成年哺乳动物中，A₂A 受体已被牵涉到颈动脉球细胞的 O₂ 感应中，而中枢 A₂A 受体可能会削弱低氧性通气过度。总之，A₂A 受体在胎儿颈动脉体和大脑的 O₂ 感应转导机制中起着至关重要的作用。出生后，中枢 A₂A 受体仍然是低氧性呼吸抑制的关键调节剂，但它们对颈动脉化学感受器的 O₂ 感应的重要性较低，尤其是在发育中的羔羊中。
