Role of Glutathione Redox State in Oxygen Sensing by Carotid Body Chemoreceptor Cells

Abstract

This article first presents some basic structural traits of the carotid body (CB) arterial chemoreceptors to understand the relationship between the arterial blood PO2 and the activation of chemoreceptor cells, which are the O2 sensing structures of the CB. Some considerations in relation to the intensity of CB blood flow and O2 consumption of the organ would allow us to define the threshold for the detection of the hypoxic stimulus, which would lead us to the cardinal theme of the article, namely whether at the PO2 levels detected by the CB there alterations in the genesis of re-active oxygen species (ROS). An alteration in the rate of ROS productionwould impinge on the glutathione system [reduced glutathione (GSH) and oxidized glutathione (GSSG)], causing modifications in the GSH/GSSG ratio that are detected by direct measurement; the GSH/GSSG system rep-resents the quantitatively most important mechanism to dispose ROS and to maintain the overall redox status or redox environment in mammalian cells.1 The relationship between GSH/GSSG and oxygen chemoreception is approached from two different points of view. We will measure GSH/GSSG levels and calculate the redox environment of the cells and correl-ation with the activity of chemoreceptor cells in normoxia and in hypoxia. We will also present data on pharmacological manipulation of the redox environment of the cells, as assessed by GSH/GSSG quotients, and pos-sible correlations with the level of activity of chemoreceptor cells. The possible mechanisms of coupling between ROS and the GSH/GSSG system to the cellular effector machineries have been reviewed.2,3