Premium
RGS4 is a negative feedback mechanism of Angiotensin II‐mediated aldosterone production in human adrenal cells
Author(s) -
Romero Damian G,
Plonczynski Maria W,
Yanes Licy L,
Washington Tanganika R,
Covington Gina,
GomezSanchez Elise P,
GomezSanchez Celso E
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a344-c
Subject(s) - aldosterone , downregulation and upregulation , endocrinology , medicine , angiotensin ii , protein kinase c , aldosterone synthase , biology , signal transduction , chemistry , receptor , renin–angiotensin system , microbiology and biotechnology , gene , blood pressure , biochemistry
Regulators of G protein signaling (RGS) increase GTPase activity of G protein accelerating the rate of G protein coupled receptor deactivation. We hypothesize that RGS4 is a negative feedback mechanism of Angiotensin II (AII)‐mediated aldosterone production in H295R human adrenal cells. AII treatment caused a 25‐fold (p < 0.01) rapid and transient increase in RGS4 mRNA expression after 3 hr treatment measured by real‐time PCR. AII‐mediated RGS4 mRNA upregulation was mimicked by PKC activation by PMA (60 % AII stimulation, p < 0.01) and completely blocked by PKC downregulation. AII‐mediated RGS4 mRNA upregulation was blocked by calcium channel blocker nifedipine (62 % inhibition, p < 0.01). RGS4 overexpression by retroviral infection decrease basal (94 % inhibition, p< 0.01) and AII‐mediated (54 % inhibition, p < 0.01) aldosterone production without modifying cortisol secretion. In reporter assays, RGS4 decrease (48 % inhibition, p < 0.01) AII‐mediated increase in aldosterone synthase expression. RGS4 is upregulated by AII in adrenal cells through calcium and PKC signaling pathways. RGS4 overexpression specifically decrease aldosterone secretion through aldosterone synthase downregulation. In conclusion, RGS4 is a negative feedback modulator of AII‐mediated aldosterone secretion that could be involved in AII signaling desensitization. Alterations in RGS4 levels could play an critical role in syndromes of hyper‐ or hypo‐aldosteronism. Supported by Dept. of Veterans Affairs and NIH grants HL27255 and HL75321.