Membrane mineralocorticoid receptor explained

Membrane mineralocorticoid receptors (mMRs) or membrane aldosterone receptors are a group of receptors which bind and are activated by mineralocorticoids such as aldosterone.^{[1] [2]} Unlike the classical nuclear mineralocorticoid receptor (MR), which mediates its effects via genomic mechanisms, mMRs are cell surface receptors which rapidly alter cell signaling via modulation of intracellular signaling cascades. The identities of the mMRs have yet to be fully elucidated, but are thought to include membrane-associated classical MRs^{[3] [4]} as well as yet-to-be-characterized G protein-coupled receptors (GPCRs).^[5] Rapid effects of aldosterone were found not be reversed by the MR antagonist spironolactone, indicating additional receptors besides just the classical MR.^{[6] [7]} It has been estimated that as much as 50% of the rapid actions of aldosterone are mediated by mMRs that are not the classical MR, based on findings of insensitivity to classical mR antagonists.

mMRs, along with membrane glucocorticoid receptors (mGRs), have been implicated in the rapid effects of mineralocorticoids in the early central stress response.^{[8] [9]} Aldosterone has been found to have rapid non-genomic effects in the central nervous system,^[10] the kidneys,^{[11] [12]} the cardiovascular system,^[13] and the colon.

GPER, also known as GPR30, binds and is activated by aldosterone, and may be considered an mMR, although it also binds and is activated by estradiol and is generally described as a membrane estrogen receptor (mER).^[14]

See also

• Membrane steroid receptor

Notes and References

1. Dooley R, Harvey BJ, Thomas W . Non-genomic actions of aldosterone: from receptors and signals to membrane targets . Mol. Cell. Endocrinol. . 350 . 2 . 223–34 . 2012 . 21801805 . 10.1016/j.mce.2011.07.019 . 24630510 .
2. Groeneweg FL, Karst H, de Kloet ER, Joëls M . Mineralocorticoid and glucocorticoid receptors at the neuronal membrane, regulators of nongenomic corticosteroid signalling . Mol. Cell. Endocrinol. . 350 . 2 . 299–309 . 2012 . 21736918 . 10.1016/j.mce.2011.06.020 . 23048944 .
3. de Kloet ER, Karst H, Joëls M . Corticosteroid hormones in the central stress response: quick-and-slow . Front Neuroendocrinol . 29 . 2 . 268–72 . 2008 . 18067954 . 10.1016/j.yfrne.2007.10.002 . 15094025 .
4. Joëls M, Karst H, DeRijk R, de Kloet ER . The coming out of the brain mineralocorticoid receptor . Trends Neurosci. . 31 . 1 . 1–7 . 2008 . 18063498 . 10.1016/j.tins.2007.10.005 . 5762688 .
5. Funder JW . The nongenomic actions of aldosterone . Endocr. Rev. . 26 . 3 . 313–21 . 2005 . 15814845 . 10.1210/er.2005-0004 . free .
6. Mihailidou AS, Funder JW . Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular system . Steroids . 70 . 5–7 . 347–51 . 2005 . 15862816 . 10.1016/j.steroids.2005.02.004 . 43782472 .
7. Wendler A, Albrecht C, Wehling M . Nongenomic actions of aldosterone and progesterone revisited . Steroids . 77 . 10 . 1002–6 . 2012 . 22285849 . 10.1016/j.steroids.2011.12.023 . 28968323 .
8. Sarabdjitsingh RA, Joëls M, de Kloet ER . Glucocorticoid pulsatility and rapid corticosteroid actions in the central stress response . Physiol. Behav. . 106 . 1 . 73–80 . 2012 . 21971364 . 10.1016/j.physbeh.2011.09.017 . 32448734 .
9. Groeneweg FL, Karst H, de Kloet ER, Joëls M . Rapid non-genomic effects of corticosteroids and their role in the central stress response . J. Endocrinol. . 209 . 2 . 153–67 . 2011 . 21357682 . 10.1530/JOE-10-0472 . free .
10. Lösel RM, Wehling M . Classic versus non-classic receptors for nongenomic mineralocorticoid responses: emerging evidence . Front Neuroendocrinol . 29 . 2 . 258–67 . 2008 . 17976711 . 10.1016/j.yfrne.2007.09.002 . 19205927 .
11. Thomas W, Harvey BJ . Mechanisms underlying rapid aldosterone effects in the kidney . Annu. Rev. Physiol. . 73 . 335–57 . 2011 . 20809792 . 10.1146/annurev-physiol-012110-142222 .
12. Harvey BJ, Alzamora R, Stubbs AK, Irnaten M, McEneaney V, Thomas W . Rapid responses to aldosterone in the kidney and colon . J. Steroid Biochem. Mol. Biol. . 108 . 3–5 . 310–7 . 2008 . 17951051 . 10.1016/j.jsbmb.2007.09.005 . 30197782 .
13. Vinson GP, Coghlan JP . Expanding view of aldosterone action, with an emphasis on rapid action . Clin. Exp. Pharmacol. Physiol. . 37 . 4 . 410–6 . 2010 . 20409082 . 10.1111/j.1440-1681.2010.05352.x . 46512893 . free .
14. Meinel S, Gekle M, Grossmann C . Mineralocorticoid receptor signaling: crosstalk with membrane receptors and other modulators . Steroids . 91 . 3–10 . 2014 . 24928729 . 10.1016/j.steroids.2014.05.017 . 35896263 .