General redox environment and carotid body chemoreceptor function

Abstract

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 (E(GSH); 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 E(GSH) and the activity of chemoreceptor cells. The independence of chemoreceptor cell activity from the E(GSH) 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 E(GSH) in all tissues assayed.

Early and late administration of MnTE-2-PyP5+ in mitigation and treatment of radiation-induced lung damage

“…It has been suggested that proinflammatory cytokines (IL-1, IL-6) may be responsible for sensitization of oxygen sensing of chemoreceptors as the rat carotid artery body expresses interleukin receptors [74, 75]. In contrast, ROS do not seem to be involved in modulating chemoreceptor activity [76]. MnTE-2-PyP 5+ obviously decreases IL-1 induced myocardial depression [77] and protects NIT-1 insulinoma cells from IL-1 induced cytotoxicity [78].…”

A revisit to O2 sensing and transduction in the carotid body chemoreceptors in the context of reactive oxygen species biology

“…In a recent article of Perez-Vizcaino laboratory (Frazziano et al, submitted) it is reported that PKC activates phosphorylation of p47 phox and activation of NADPH oxidase with the ROS generated playing a necessary role in controlling the open probability of Kv channels in PASMC; in addition they also present evidence suggestive that increased mitochondrial ROS production could play a critical role in the activation of neutral sphingomyelinase. In our laboratory, we have tested a wide variety of reducing and oxidizing agents (Sanz-Alfayate et al, 2001;Gonzalez et al, 2004a,b;Agapito et al, 2009) and we could not establish a relationship between the general redox status of the cell and the activity of chemoreceptor cells. In a recent study (Gomez-Niño et al, 2009a,b) we aimed to manipulate mitochondrial rate of ROS production and redox status with the use of metabolic poisons and uncouplers in isolation and in the presence of N-acetylcysteine.…”

Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

“…It is, however, likely that localized changes in ROS may act to control selective functions in microdomains within the cell (667) and that this potential action would be masked by the relatively poor resolution of present technology (17). One such source of ROS localized close to plasmalemmal K + channels of type I cells (482) is the extramitochondrial, membrane bound, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) complex, which produces O 2 − and H 2 O 2 , in proportion to Po 2 (8).…”