Protein mineralocorticoid receptor

Microtubule Associated Proteins Mineralcorticoids Mineralocorticoid Receptor (MR)... 

Verrijdt, G., Haelens, A., Schoenmakers, E., Rombauts, W., and Claessens, F. (2002) Comparative analysis of the influence of the high-mobility group box 1 protein on DNA binding and transcriptional activation by the androgen, glucocorticoid, progesterone and mineralocorticoid receptors. Biochem. J. 361, 97-103. 

The mechanism by which Na" is reabsorbed in coupled exchange with and K+ in the collecting duct has been discussed previously that is, Na+-driven K+ secretion is partially under mineralocorticoid control. Aldosterone and other compounds with mineralocorticoid activity bind to a specific mineralocorticoid receptor in the cytoplasm of late distal tubule cells and of principal cells of the collecting ducts. This hormone-receptor complex is transported to the cell nucleus, where it induces synthesis of multiple proteins that are collectively called aldosterone-induced proteins. The precise mechanisms by which these proteins enhance Na+ transport are incompletely understood. However, the net effect is to increase Na" entry across apical cell membranes and to increase basolateral membrane Na+-K+-ATPase activity and synthesis. 

Figure 12.6 Mechanism of action of mineralocortjcoid receptor antagonists in the collecting tubule. Aldosterone enters the tubular cell by the basolateral surface and binds to a specific mineralocorticoid receptor (MNR) in the cytoplasm. The hormone receptor complex triggers the production of an aldosterone-induced protein (AlP) by the cell nucleus (NUC). The AIP acts on the sodium ion channel (ic) to augment the transport of Na+across the basolateral membrane and in to the cell. An increase in AIP activity leads to the recruitment of dormant sodium ion channels and Na pumps (P) in the cell membrane. AIP also leads to the synthesis of new channels and pumps within the cell. The increase in Na+conductance causes electrical changes in the luminal membrane that favour the excretion of intracellular cations, such as K+and H-h. Spironolactone competes with aldosterone for the binding site on the MNR and forms a complex which does not excite the production of AIP by the nucleus.

Angiotensin II has a variety of effects. By constricting blood vessels it raises blood pressure, and by stimulating thirst centers in the brain it increases blood volume. Both angiotensins II and III also act on the adrenal gland to promote the synthesis and release of aldosterone. Most of the effects of angiotension II are mediated by 359-residue seven-helix G-protein linked receptors which activate phospholipase C.p q qr Like other steroid hormones aldosterone acts,via mineralocorticoid receptors, to control transcription of a certain set of proteins. The end effect is to increase the transport of Na+ across the renal tubules and back into the blood. Thus, aldosterone acts to decrease the loss of Na+ from the body. It promotes retention of water and raises... 

Alterations in the glucocorticoid molecule influence its affinity for glucocorticoid and mineralocorticoid receptors as well as its protein-binding avidity, side chain stability, rate of reduction, and metabolic products. Halogenation at the 9 position, unsaturation of the a1-2 bond of... 

The steroid receptor family inclndes androgen receptors (AR), estrogen receptors (ER, a. and (3), progesterone receptors (PR, A and B), glncocorticoid receptors (GR), and mineralocorticoid receptors (MR). Traditional models propose that, upon binding their hormonal ligand, the receptors release heat shock proteins like hsp90, translocate into the nucleus, and bind as homodimers to imperfect palindromic response elements at upstream promoter sites. 

FIGURE 28-6 Effects of aldosterone on late distal tubule and collecting duct and diuretic mechanism of aldosterone antagonists. AIP, aldosterone-induced proteins ALDO, aldosterone MR, mineralocorticoid receptor CH, ion channel 1, activation of membrane-bound Na channels 2, redistribution of Na" channels from cytosol to membrane 3, de novo synthesis of Na+channels 4, activation of membrane-bound Na , K -ATPase 5, redistribution of Na , K -ATPase from cytosol to membrane 6, de novo synthesis of Na, K -ATPase 7, changes in permeability of tight junctions 8, increased mitochondrial production of ATP. BL and LM indicate basolateral and luminal membranes, respectively. 

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