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Am J Physiol Cell Physiol 276: C593-C601, 1999;
0363-6143/99 $5.00
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Vol. 276, Issue 3, C593-C601, March 1999

NADPH oxidase inhibition does not interfere with low PO2 transduction in rat and rabbit CB chemoreceptor cells

A. Obeso, A. Gómez-Niño, and C. Gonzalez

Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular, Consejo Superior Investigaciones Científicas, Facultad de Medicina, Universidad de Valladolid, 47005 Valladolid, Spain

The aim of the present work was to elucidate the role of NADPH oxidase in hypoxia sensing and transduction in the carotid body (CB) chemoreceptor cells. We have studied the effects of several inhibitors of NADPH oxidase on the normoxic and hypoxia-induced release of [3H]catecholamines (CA) in an in vitro preparation of intact CB of the rat and rabbit whose CA deposits have been labeled by prior incubation with the natural precursor [3H]tyrosine. It was found that diphenyleneiodonium (DPI; 0.2-25 µM), an inhibitor of NADPH oxidase, caused a dose-dependent release of [3H]CA from normoxic CB chemoreceptor cells. Contrary to hypoxia, DPI-evoked release was only partially Ca2+ dependent. Concentrations of DPI reported to produce full inhibition of NADPH oxidase in the rat CB did not prevent the hypoxic release response in the rat and rabbit CB chemoreceptor cells, as stimulation with hypoxia in the presence of DPI elicited a response equaling the sum of that produced by DPI and hypoxia applied separately. Neopterin (3-300 µM) and phenylarsine oxide (0.5-2 µM), other inhibitors of NADPH oxidase, did not promote release of [3H]CA in normoxic conditions or affect the response elicited by hypoxia. On the basis of effects of neopterin and phenylarsine oxide, it is concluded that NADPH oxidase does not appear to play a role in oxygen sensing or transduction in the rat and rabbit CB chemoreceptor cells in vitro and, in the context of the present study, that DPI effects are not related to NADPH oxidase inhibition.

hypoxia; reactive oxygen species; diphenyleneiodonium; neopterin; phenylarsine oxide; carotid body; partial pressure of oxygen


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