Membrane mineralocorticoid receptor

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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. [1] [2] 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). [1] [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. [7]

mMRs, along with membrane glucocorticoid receptors (mGRs), have been implicated in the rapid effects of mineralocorticoids in the early central stress response. [2] [3] [4] [8] [9] Aldosterone has been found to have rapid non-genomic effects in the central nervous system, [10] the kidneys, [1] [11] [12] the cardiovascular system, [6] [13] and the colon. [1] [12]

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). [7] [14]

See also

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References

  1. 1 2 3 4 5 Dooley R, Harvey BJ, Thomas W (2012). "Non-genomic actions of aldosterone: from receptors and signals to membrane targets". Mol. Cell. Endocrinol. 350 (2): 223–34. doi:10.1016/j.mce.2011.07.019. PMID   21801805. S2CID   24630510.
  2. 1 2 3 Groeneweg FL, Karst H, de Kloet ER, Joëls M (2012). "Mineralocorticoid and glucocorticoid receptors at the neuronal membrane, regulators of nongenomic corticosteroid signalling". Mol. Cell. Endocrinol. 350 (2): 299–309. doi:10.1016/j.mce.2011.06.020. PMID   21736918. S2CID   23048944.
  3. 1 2 de Kloet ER, Karst H, Joëls M (2008). "Corticosteroid hormones in the central stress response: quick-and-slow". Front Neuroendocrinol. 29 (2): 268–72. doi:10.1016/j.yfrne.2007.10.002. PMID   18067954. S2CID   15094025.
  4. 1 2 Joëls M, Karst H, DeRijk R, de Kloet ER (2008). "The coming out of the brain mineralocorticoid receptor". Trends Neurosci. 31 (1): 1–7. doi:10.1016/j.tins.2007.10.005. PMID   18063498. S2CID   5762688.
  5. ↑ Funder JW (2005). "The nongenomic actions of aldosterone". Endocr. Rev. 26 (3): 313–21. doi: 10.1210/er.2005-0004 . PMID   15814845.
  6. 1 2 Mihailidou AS, Funder JW (2005). "Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular system". Steroids. 70 (5–7): 347–51. doi:10.1016/j.steroids.2005.02.004. PMID   15862816. S2CID   43782472.
  7. 1 2 3 Wendler A, Albrecht C, Wehling M (2012). "Nongenomic actions of aldosterone and progesterone revisited". Steroids. 77 (10): 1002–6. doi:10.1016/j.steroids.2011.12.023. PMID   22285849. S2CID   28968323.
  8. ↑ Sarabdjitsingh RA, Joëls M, de Kloet ER (2012). "Glucocorticoid pulsatility and rapid corticosteroid actions in the central stress response". Physiol. Behav. 106 (1): 73–80. doi:10.1016/j.physbeh.2011.09.017. PMID   21971364. S2CID   32448734.
  9. ↑ Groeneweg FL, Karst H, de Kloet ER, Joëls M (2011). "Rapid non-genomic effects of corticosteroids and their role in the central stress response". J. Endocrinol. 209 (2): 153–67. doi: 10.1530/JOE-10-0472 . PMID   21357682.
  10. ↑ Lösel RM, Wehling M (2008). "Classic versus non-classic receptors for nongenomic mineralocorticoid responses: emerging evidence". Front Neuroendocrinol. 29 (2): 258–67. doi:10.1016/j.yfrne.2007.09.002. PMID   17976711. S2CID   19205927.
  11. ↑ Thomas W, Harvey BJ (2011). "Mechanisms underlying rapid aldosterone effects in the kidney". Annu. Rev. Physiol. 73: 335–57. doi:10.1146/annurev-physiol-012110-142222. PMID   20809792.
  12. 1 2 Harvey BJ, Alzamora R, Stubbs AK, Irnaten M, McEneaney V, Thomas W (2008). "Rapid responses to aldosterone in the kidney and colon". J. Steroid Biochem. Mol. Biol. 108 (3–5): 310–7. doi:10.1016/j.jsbmb.2007.09.005. PMID   17951051. S2CID   30197782.
  13. ↑ Vinson GP, Coghlan JP (2010). "Expanding view of aldosterone action, with an emphasis on rapid action". Clin. Exp. Pharmacol. Physiol. 37 (4): 410–6. doi:10.1111/j.1440-1681.2010.05352.x. PMID   20409082. S2CID   46512893.
  14. ↑ Meinel S, Gekle M, Grossmann C (2014). "Mineralocorticoid receptor signaling: crosstalk with membrane receptors and other modulators". Steroids. 91: 3–10. doi:10.1016/j.steroids.2014.05.017. PMID   24928729. S2CID   35896263.


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