ArticleScientific reports2026
Molecular mechanism of p-Coumaric acid in the regulation of AQP2 function through the activation of calcium-sensing receptor signaling.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The hormone vasopressin (AVP) controls renal water reabsorption by modulating the expression and trafficking of the water channel aquaporin-2 (AQP2) through the activation of the cAMP/PKA signal transduction pathway. Previous studies revealed that Olive Leaf Extract (OLE) counteracts the vasopressin-dependent AQP2 functions by stimulating the calcium-sensing receptor (CaSR). Here, the biological activities of p-Coumaric acid, a selective polyphenol in OLE, were investigated. Stimulation of renal collecting duct MCD4 cells with p-Coumaric acid at a concentration of 1 nM caused a significant intracellular calcium release. NPS-2143, a selective CaSR antagonist, abolished this increase. Molecular docking analysis revealed that p-Coumaric acid can form binding interactions with the binding pocket of Tecalcet, a known CaSR activator, likely suggesting that p-Coumaric acid may stimulate the CaSR. Confocal analysis and immunoblotting experiments showed that p-Coumaric acid impaired the DDAVP-dependent membrane expression of AQP2 and the consequent increase of the osmotic water permeability (Pf). Additionally, Fluorescence Resonance Energy Transfer (FRET) experiments demonstrated that p-Coumaric acid prevented the DDAVP-induced cAMP generation, consequently attenuating the AQP2 phosphorylation at serine 256. Together, these findings suggest that p-Coumaric acid may antagonize the effects of vasopressin, possibly by binding to and stimulating the CaSR.
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