8.A.80 The Renin Receptor (RR) Family 

The renin receptor functions as a renin and prorenin cellular receptor. It may mediate renin-dependent cellular responses by activating ERK1 and ERK2. By increasing the catalytic efficiency of renin in AGT/angiotensinogen conversion to angiotensin I, it may also play a role in the renin-angiotensin system (Nguyen et al. 2002).

(Pro)renin receptor (PRR) is highly expressed in the distal nephron. Administration of PRO20, a decoy peptide antagonist of PRR, to K⁺-loaded animals elevated plasma K⁺ levels and decreased urinary K⁺ excretion, accompanied by suppressed aldosterone excretion (Xu et al. 2016).  High K⁺ downregulates Na⁺-Cl^- cotransporter (NCC) expression but upregulated the renal outer medullary K⁺ channel (ROMK), calcium-activated potassium channel subunit alpha-1 (α-BK), α-Na⁺-K⁺-ATPase (α-NKA), and epithelial Na⁺ channel subunit beta (β-ENaC), all of which were blunted by PRO20. Following HK, urinary but not plasma renin was upregulated, which was blunted by PRO20. The same experiments performed using adrenalectomized (ADX) rats yielded similar results.  Spironolactone treatment in high K⁺-loaded ADX rats attenuated kaliuresis but promoted natriuresis associated with the suppressed responses of β-ENaC, α-NKA, ROMK, and α-BK protein expression. Thus, renal PRR regulates K⁺ homeostasis through a local mechanism involving the intrarenal renin-angiotensin-aldosterone system and coordinates the regulation of several membrane Na⁺ and K⁺ transporting proteins (Xu et al. 2016).