Inhibition of aldosterone release by hypoxia in vitro: interaction with carbon monoxide.
Inhibition of aldosterone release by hypoxia in vitro: interaction with carbon monoxide.
复制标题
体外缺氧抑制醛固酮释放：与一氧化碳的相互作用。
DOI：
10.1152/jappl.1994.76.2.689
复制
发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Jankowski,B
中科院分区：
文献类型：
--
作者：
Raff,H;Jankowski,B
We have demonstrated that the aldosteronogenic pathway of the zona glomerulosa is unusually sensitive to modest changes in PO2 (Michaelis constant for O2 approximately 95 Torr). The current study evaluated the interaction of CO (the classic ligand for P-450 enzymes) and the decreases in O2 on aldosteronogenesis in vitro. Bovine adrenocortical zona glomerulosa cells were incubated for 2 h and stimulated with either adenosine 3′,5′-cyclic monophosphate (cAMP) or angiotensin II. Ten and 20% CO led to significant decreases in cAMP- and angiotensin II-stimulated aldosteronogenesis. The combination of 20% CO and moderate decreases in PO2 (from approximately 140 to approximately 100 Torr) led to an interactive decrease in aldosterone production. The conversion of corticosterone to aldosterone catalyzed by aldosterone synthase, which is the site of O2 sensitivity, was not significantly inhibited by CO. We conclude that the aldosterone pathway is not exceptionally sensitive to CO compared with other steroidogenic pathways. This observation suggests that the unique O2-sensitive properties of the aldosterone pathway located primarily within aldosterone synthase may not reside in its CO binding site (i.e., heme).
