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RECEPTORS AND SIGNAL TRANSDUCTION
1Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid, Facultad de Medicina; 2Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC); and 3Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Valladolid, Spain
Submitted 22 October 2008 ; accepted in final form 7 January 2009
Carotid body (CB) chemoreceptor cells detect physiological levels of hypoxia and generate a hyperventilation, homeostatic in nature, aimed to minimize the deleterious effects of hypoxia. Intimate mechanisms involved in oxygen sensing in chemoreceptor cells remain largely unknown, but reactive oxygen species (ROS) had been proposed as mediators of this process. We have determined glutathione levels and calculated glutathione redox potential (EGSH; indicator of the general redox environment of cells) in rat diaphragms incubated in the presence of oxidizing agents of two types: nonpermeating and permeating through cell membranes; in the latter group, unspecific oxidants and inhibitors of ROS-disposing enzymes were used. Selected concentrations of oxidizing agents were tested for their ability to modify the normoxic and hypoxic activity of chemoreceptor cells measured in vitro as their rate of release of neurotransmitters. Results evidence variable relationships between EGSH and the activity of chemoreceptor cells. The independence of chemoreceptor cell activity from the EGSH would imply that the ability of the CB to play its homeostatic role is largely preserved in any pathological or toxicological contingency causing oxidative stress. Consistent with this suggestion, it was also found that CB-mediated hypoxic hyperventilation was not altered by treatment of intact animals with agents that markedly decreased the EGSH in all tissues assayed.
oxygen sensing; carotid body; reactive oxygen species; hypoxia; reduced glutathione, oxidized glutathione; catecholamine; ventilation
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