AMP-activated protein kinase underpins hypoxic pulmonary vasoconstriction and carotid body excitation by hypoxia in mammals.
In order to maintain tissue partial pressure of oxygen (P(O(2))) within physiological limits, vital homeostatic mechanisms monitor O(2) supply and respond to a fall in P(O(2)) by altering respiratory and circulatory function, and the capacity of the blood to transport O(2). Two systems that are key to this process in the acute phase are the pulmonary arteries and the carotid bodies. Hypoxic pulmonary vasoconstriction is driven by mechanisms intrinsic to the pulmonary arterial smooth muscle and endothelial cells, and aids ventilation-perfusion matching in the lung by diverting blood flow from areas with an O(2) deficit to those that are rich in O(2). By contrast, a fall in arterial P(O(2)) precipitates excitation-secretion coupling in carotid body type I cells, increases sensory afferent discharge from the carotid body and thereby elicits corrective changes in breathing patterns via the brainstem. There is a general consensus that hypoxia inhibits mitochondrial oxidative phosphorylation in these O(2)-sensing cells over a range of P(O(2)) values that has no such effect on other cell types. However, the question remains as to the identity of the mechanism that underpins hypoxia-response coupling in O(2)-sensing cells. Here, I lay out the case in support of a primary role for AMP-activated protein kinase in mediating chemotransduction by hypoxia.
Evans
A Mark
AM
Division of Biomedical Sciences, School of Biology, University of St Andrews, St Andrews, Fife KY16 9TS, UK. ame3@st-andrews.ac.uk
D055372:AMP-Activated Protein Kinases; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002344:Carotid Body / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply; D008322:Mammals; D009097:Multienzyme Complexes / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011651:Pulmonary Artery / Q000502:physiology; D011652:Pulmonary Circulation / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014661:Vasoconstriction / Q000502:physiology*
D009097:Multienzyme Complexes; D017382:Reactive Oxygen Species; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D010100:Oxygen; D002118:Calcium