The Impact and Mechanism of Angiotensin II Type 2 Receptor（AT2） on Aldosterone Secretion and Adrenocortical Cell Apoptosis
Date Issued
2004
Date
2004
Author(s)
Chu, Pei-Lun
DOI
zh-TW
Abstract
Renin-Angiotensin-Aldosterone system (RAA system) controls the hemodynamic status, body fluid and electrolyte balance in human body. In the system, ANGII is a key hormone which has 2 main receptor subtypes, AT1 and AT2. Most physiological effects of ANGII were mediated by AT1. It constricts arteries, elevates blood pressure and also stimulates adrenal gland to secret aldosterone. However, the role of AT2 in adrenal gland is not well studied as AT1.
AT2, a G-protein coupled receptor has 7 transmembrane domains, is widely expressed during fetal development. It regresses or even disappears rapidly in early postnatal period except some limited tissue like limbic system, several thalamic nucleus, adrenal medulla, zona glomerulosa and uterine myometrium etc. The general understanding of its functions are inhibition of cell growth, promotion of cell differentiation or cell apoptosis, mediates neural cell remodeling, inhibition of angiogenesis and counteracts AT1’s effects. In adult adrenal gland, 40% of AT2 is presented in zona glomerulosa; however, the significance of its persistent expression is unknown.
We established stable H295R cell line and aldosterone concentration was detected by radioimmunoassay (RIA) which was corrected by total protein amount. CYP11B2 mRNA and AT2 protein expression were detected by RT-PCR and Western blot later. Cell apoptosis was analyzed by flow cytometry.
After ANGII stimulation, aldosterone was detectable since 24th hour and lasted up to 72 hours. The ANGII induced aldosterone secretion was 61% suppressed by AT1 blocker, valsartan; but AT2 blocker, PD123319 has no effect on it. However, co-treatment with valsartan and PD123319 could suppress aldosterone secretion almost totally.
CYP11B2 mRNA expression could be detected since 2nd hour and maxially expressed at 8th hour after 1μM ANGII treatment. Valsartan suppressed CYP11B2 mRNA expression, whereas PD123319 alone has no impact on it. If pretreated with valsartan and PD123319 simultaneously, the expression of CYP11B2 mRNA was suppressed to basal level as control group.The mRNA change seems to correlate with the aldosterone secretion change. Although CGP42112A up-regulates CYP11B2 mRNA expression, it does not interfer aldosterone secretion as PD123319 does. By Western blot, AT2 expression was not altered by every tested condition and the flow cytometry showed no obvious apoptosis.
In conclusion, AT1, is the main receptor for aldosterone secretion through CYP11B2；AT2 is involved too, but there might be a “cross talk”between AT1 and AT2. It does not function via CYP11B2 totally or even with post-transcription, translation modification by AT1 or other pathways. So far, AT2 mediated cell apoptosis was not observed in H295R cell.
Subjects
第二型血管張力素第二型受器（AT2）
腎素-血管加壓素-醛固酮系統
第二型血管張力素（ANGII）
人類腎上腺皮質腫瘤細胞（H295R cell）
醛固酮
細胞凋亡
醛固酮合成酵素（CYP11B2）
Renin-Angiotensin-Aldosterone system (RAA system)
angiotensin II（ANGII）
human adrenocortical carcinoma cell（H295R cell）
angiotensin II type 2 receptor（AT2）
aldosterone
aldosterone synthase（CYP11B2）
apoptosis
Type
text
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