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Effects of reducing agents on glutathione metabolism and the function of carotid body chemoreceptor cells.

Abstract：

:Two current hypotheses of O2 sensing in the carotid body (CB) chemoreceptors suggest participation of oxygen reactive (ROS) species, but they are mechanistically opposed. One postulates that hypoxia decreases ROS levels; the other that hypoxia increases them. Yet, both propose that the ensuing alteration in the cellular redox environment is the key signal triggering hypoxic chemoreception. Since the glutathione redox pair is the main cellular buffer for ROS and the main determinant of the general redox environment of the cells, a way to test whether ROS participate in chemoreception is to determine glutathione levels and to correlate them with the activity of CB chemoreceptor cells. We found that hypoxia does not alter the glutathione reduction potential but that it activates chemoreceptor cell neurosecretion. Incubation of tissues with reduced glutathione increases the glutathione-reducing potential but does not activate chemoreceptor cells in normoxia nor does it modify hypoxic activation. Like reduced glutathione, N-acetylcysteine promoted a general reducing environment in the cells without alteration of chemoreceptor cell activity. N-(mercaptopropionyl)-glycine, like the two previous agents, increases the reduction potential of glutathione. In contrast, the compound activated chemoreceptor cells in normoxia, promoting a dose- and Ca(2+)-dependent neurosecretion and a potentiation of the hypoxic responses. The existence of multiple relationships between glutathione reduction potential in the cells and their activity indicates that the general cellular redox environment is not a factor determining chemoreceptor cell activation. It cannot be excluded that the local redox environments of restricted microdomain(s) in the cells with specific regulating mechanisms are important signals for chemoreceptor cell activity.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Gonzalez C,Sanz-Alyayate G,Agapito MT,Obeso A

doi

10.1515/BC.2004.021

keywords:

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

265-74

issue

3-4

eissn

1431-6730

issn

1437-4315

journal_volume

385

pub_type

杂志文章

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Effects of reducing agents on glutathione metabolism and the function of carotid body chemoreceptor cells.