Obeso A, Gómez-Niño A, Gonzalez C
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.
Am J Physiol. 1999 Mar;276(3):C593-601. doi: 10.1152/ajpcell.1999.276.3.C593.
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 microM), 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 microM) and phenylarsine oxide (0.5-2 microM), 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.
本研究的目的是阐明NADPH氧化酶在颈动脉体（CB）化学感受器细胞缺氧感知和转导中的作用。我们研究了几种NADPH氧化酶抑制剂对大鼠和家兔完整CB体外制备物中常氧和缺氧诱导的[3H]儿茶酚胺（CA）释放的影响，这些CB的CA沉积物已通过预先与天然前体[3H]酪氨酸孵育进行标记。发现NADPH氧化酶抑制剂二亚苯基碘鎓（DPI；0.2 - 25 μM）可引起常氧CB化学感受器细胞剂量依赖性地释放[3H]CA。与缺氧情况相反，DPI诱发的释放仅部分依赖于Ca2+。据报道，在大鼠CB中能完全抑制NADPH氧化酶的DPI浓度并不能阻止大鼠和家兔CB化学感受器细胞的缺氧释放反应，因为在DPI存在下用缺氧刺激引发的反应等于单独应用DPI和缺氧所产生反应之和。NADPH氧化酶的其他抑制剂新蝶呤（3 - 300 μM）和氧化苯胂（0.5 - 2 μM）在常氧条件下不会促进[3H]CA的释放，也不影响缺氧引发的反应。基于新蝶呤和氧化苯胂的作用，得出结论：在体外大鼠和家兔CB化学感受器细胞中，NADPH氧化酶似乎在氧感知或转导中不起作用，并且在本研究的背景下，DPI的作用与NADPH氧化酶抑制无关。
