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]
^ abcdeDooley 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.
^ abcGroeneweg 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.
^ abde 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.
^ abJoëls 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.
^Funder JW (2005). "The nongenomic actions of aldosterone". Endocr. Rev. 26 (3): 313–21. doi:10.1210/er.2005-0004. PMID 15814845.
^ abMihailidou 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.
^ abcWendler 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.
^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.
^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.
^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.
^ abHarvey 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.
^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.
^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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