Abstract
Vasopressin (AVP) increases water permeability in the renal collecting duct through the regulation of aquaporin-2 (AQP2) trafficking. Several disorders, including hypertension and inappropriate antidiuretic hormone secretion (SIADH), are associated with abnormalities in water homeostasis. It has been shown that certain phytocompounds are beneficial to human health. Here, the effects of the Olive Leaf Extract (OLE) have been evaluated using in vitro and in vivo models. Confocal studies showed that OLE prevents the vasopressin induced AQP2 translocation to the plasma membrane in MCD4 cells and rat kidneys. Incubation with OLE decreases the AVP-dependent increase of the osmotic water permeability coefficient (Pf). To elucidate the possible effectors of OLE, intracellular calcium was evaluated. OLE increases the intracellular calcium through the activation of the Calcium Sensing Receptor (CaSR). NPS2143, a selective CaSR inhibitor, abolished the inhibitory effect of OLE on AVP-dependent water permeability. In vivo experiments revealed that treatment with OLE increases the expression of the CaSR mRNA and decreases AQP2 mRNA paralleled by an increase of the AQP2-targeting miRNA-137. Together, these findings suggest that OLE antagonizes vasopressin action through stimulation of the CaSR indicating that this extract may be beneficial to attenuate disorders characterized by abnormal CaSR signaling and affecting renal water reabsorption.
Highlights
Vasopressin (AVP) increases water permeability in the renal collecting duct through the regulation of aquaporin-2 (AQP2) trafficking
These findings suggest that Olive Leaf Extract (OLE) antagonizes vasopressin action through stimulation of the Calcium Sensing Receptor (CaSR) indicating that this extract may be beneficial to attenuate disorders characterized by abnormal CaSR signaling and affecting renal water reabsorption
antidiuretic hormone vasopressin (AVP) binds its cognate V2R receptor localized at the basolateral membrane of renal principal cells thereby activating the cAMP signal pathway that results in the translocation of the aquaporin-2 (AQP2) bearing vesicles from an intracellular pool to the apical plasma membrane where water reabsorption occurs
Summary
Vasopressin (AVP) increases water permeability in the renal collecting duct through the regulation of aquaporin-2 (AQP2) trafficking. In vivo experiments revealed that treatment with OLE increases the expression of the CaSR mRNA and decreases AQP2 mRNA paralleled by an increase of the AQP2-targeting miRNA-137 Together, these findings suggest that OLE antagonizes vasopressin action through stimulation of the CaSR indicating that this extract may be beneficial to attenuate disorders characterized by abnormal CaSR signaling and affecting renal water reabsorption. Abbreviations OLE Olive leaf extract AVP Vasopressin AQP2 Aquaporin-2 SIADH Inappropriate antidiuretic hormone secretion CaSR Calcium sensing receptor SHR Spontaneously hypertensive rats cAMP Cyclic adenosine monophosphate FK Forskolin FBS Fetal bovine serum V2R Vasopressin receptor 2 dDAVP Desmopressin. The effects of the olive leaf extract, obtained from the local Coratina cultivar, were evaluated on vasopressin-induced AQP2 function in renal collecting duct MCD4 cells stably expressing AQP2 and in dDAVP treated rats injected with the extract. This effect appears to be related to OLE-induced activation of the CaSR, a receptor known to have a negative interplay with the vasopressin receptor[12]
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