1. Model of regulatory pathways for the mineralocorticoid receptor (MR) in intercalated cells: hyperkalemia and volume depletion.
Model of regulatory pathways for the mineralocorticoid receptor (MR) in intercalated cells: hyperkalemia and volume depletion. This figure depicts pathways that involve the differential phosphorylation state of the MR in principal versus intercalated cells (type A-IC; type B-IC), that are likely the key to the distinct responses of these cells in two different scenarios. (A) The first scenario involves conditions when only aldosterone is present (as in hyperkalemia). In this case, hyperkalemia leads to aldosterone secretion while no angiotensin II is present. Here, MR is phosphorylated in intercalated but not in principal cells. These conditions lead to aldosterone-mediated Na+ reabsorption via the epithelial sodium channel in principal cells, which drives K+ secretion also in principal cells. (B) In contrast, when both angiotensin II and aldosterone are present (as in intravascular volume depletion), the MR is dephosphorylated downstream of angiotensin II, and the activity of this receptor is thus restored in intercalated cells. In addition, as a result of aldosterone signaling both pendrin and H+-ATPase are upregulated, and in turn there is a decrease drive for K+ secretion. Modified from reference 69.
Ankita Roy et al. CJASN 2015;10:
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