Diuretic Action of Apelin-13 Mediated by Inhibiting cAMP/PKA/sPRR Pathway.

Area of Science:

• Nephrology
• Endocrinology
• Molecular Biology

Background:

• Apelin regulates salt and water balance, counteracting vasopressin (AVP).
• The precise mechanism of apelin's diuretic action, particularly in the distal nephron, remains unclear.
• The (pro)renin receptor (PRR)/soluble prorenin receptor (sPRR) system is investigated as a potential mediator.

Purpose of the Study:

• To elucidate the molecular mechanism underlying apelin's diuretic effect.
• To investigate the role of the PRR/sPRR system in apelin's action in the distal nephron.
• To identify the specific signaling pathway targeted by apelin.

Main Methods:

• Water deprivation (WD) model in vivo.
• Analysis of protein expression of aquaporin 2 (AQP2), NKCC2, PRR/sPRR, renin, and β-catenin.
• Inhibition studies using apelin-13, PKA inhibitor (H89), and β-catenin inhibitor (ICG001).
• Reversal experiments with exogenous sPRR.

Main Results:

• Apelin-13 impaired urine concentrating ability during WD, suppressing AQP2, NKCC2, PRR/sPRR, renin, and β-catenin.
• Apelin-13 blocked AVP- and 8-Br-cAMP-induced upregulation of AQP2 and PRR/sPRR.
• Inhibition of PKA and β-catenin mimicked apelin-13's effects.
• Exogenous sPRR reversed apelin-13's inhibitory effect on AVP-induced AQP2 expression.

Conclusions:

• The study defines the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/sPRR pathway in the collecting duct (CD) as the molecular target of apelin's diuretic action.
• This pathway is crucial for mediating the effects of AVP on water reabsorption.
• Apelin exerts its diuretic effect by modulating this specific signaling cascade.