Local renin-angiotensin system is involved in K+-induced aldosterone secretion from human adrenocortical NCI-H295 cells

被引:39
作者
Hilbers, U
Peters, J
Bornstein, SR
Correa, FMA
Jöhren, O
Saavedra, JM
Ehrhart-Bornstein, M
机构
[1] NICHD, NIH, Bethesda, MD 20892 USA
[2] Univ Leipzig, Dept Internal Med 3, D-7010 Leipzig, Germany
[3] Heidelberg Univ, Dept Pharmacol, D-6900 Heidelberg, Germany
[4] NIMH, Pharmacol Sect, Bethesda, MD 20892 USA
关键词
NCI-H295 cell line; renin-angiotensin system; angiotensin II; aldosterone; potassium;
D O I
10.1161/01.HYP.33.4.1025
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
NCI-H295, a human adrenocarcinoma cell line, has been proposed as a model system to define the role of the renin-angiotensin system in the regulation of aldosterone production in humans. Because the precise cellular localization of the components of the renin-angiotensin system in human adrenal cortical cells remains unclear, we investigated their localization in this defined cell system. NCI-H295 cells expressed both angiotensinogen and renin as shown by reverse transcriptase polymerase chain reaction and immunohistochemistry. Human angiotensin-converting enzyme (ACE) was not detectable by immunocytochemistry, ACE binding, or reverse transcriptase polymerase chain reaction. However, 3.5 mmol/L K+ stimulated the formation of both angiotensin I and angiotensin II 1.9- and 2.5-fold, respectively, and increased aldosterone release 3.0-fold. The K+-induced stimulation of aldosterone release was decreased by captopril and enalaprilat (24% and 26%, respectively) and by the angiotensin type 1 (AT(1))-receptor antagonist losartan (28%). Angiotensin II-induced stimulation of aldosterone release was abolished by losartan treatment. Specific [I-125]Sar1-angiotensin II binding was detected by receptor autoradiography. The binding of [I-125]Sar(1)-angiotensin II was completely displaced by the AT(1) antagonist losartan but not by the AT(2) receptor ligand PD 123319, confirming the expression of angiotensin II AT(1) receptors in NCI-H295 cells. Our results demonstrate that NCI-H295 cells express most of the components of the renin-angiotensin system. Our failure to detect ACE, however, suggests that the production of angiotensin II in NCI-H295 cells may be ACE independent. NCI-H295 cells are able to produce angiotensin II, and K+ increases aldosterone secretion in part through an angiotensin-mediated pathway. The production of angiotensin II in NCI-H295 cells demonstrates that this human cell line can be useful to characterize the role of locally produced angiotensin II in the regulation of aldosterone release.
引用
收藏
页码:1025 / 1030
页数:6
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