Characterization of a functional V_1B vasopressin receptor in the male rat kidney: evidence for cross talk between V_1B and V₂ receptor signaling pathways

Abstract

Although vasopressin V1B receptor (V1B-R) mRNA was detected in the kidney, the precise renal localization, pharmacological and physiological properties of this receptor remain unknown. Using the selective V1B agonist d[Leu4, Lys8]VP, either fluorescent or radioactive, we showed that V1B-R is mainly present in principal cells of the inner medullary collecting duct (IMCD) in the male rat kidney. Protein and mRNA expression of V1B-R were very low compared to V2 receptor (V2-R). On microdissected IMCD, d[Leu4, Lys8]VP had no effect on cAMP production but induced a dose-dependent and saturable [Ca2+]i increase mobilization with an EC50 in the nanomolar range. This effect involved both intracellular calcium mobilization and extracellular calcium influx. The selective V1B antagonist SSR149415 strongly reduced the ability of vasopressin to increase [Ca2+]i but also cAMP suggesting a cooperation between V1B-R and V2-R in IMCD cells expressing both receptors. This cooperation arises from a crosstalk between second messenger cascade involving protein kinase C rather than receptor heterodimerization as supported by potentiation of the AVP-stimulated cAMP production in HEK293 cells co-expressing the two receptor isoforms and negative results obtained by bioluminescence resonance energy transfer experiments. In vivo, only acute administration of high doses of V1B agonist triggered significant diuretic effects by contrast with injection of selective V2 agonist. This study brings new data on the localization and signaling pathways of V1B-R in the kidney, highlights a crosstalk between V1B-R and V2-R in IMCD and suggests that V1B-R may counterbalance in some pathophysiological conditions the antidiuretic effect triggered by V2-R activation.

An Octopus-Derived Peptide with Antidiuretic Activity in Rats

“…However, there is a limit to directly extrapolating the results of this experiment in rats to efficiency in humans: V2R is located in the kidney and is well known to mediate antidiuretic action by increasing the membrane trafficking of aquaporin-2 (AQP2) water channels and by increasing the protein abundance of AQP2 [ 31 , 32 ]. V1bR, the other target of CPT and desmopressin, is also functional in the kidney, although the expression level is very low [ 33 ]. Administration of a selective V1bR agonist results in a diuretic effect [ 33 ].…”

“…V1bR, the other target of CPT and desmopressin, is also functional in the kidney, although the expression level is very low [ 33 ]. Administration of a selective V1bR agonist results in a diuretic effect [ 33 ]. Therefore, the balance of V1bR activity and V2R activity should be considered when discussing renal water regulation.…”

Complementary Role of Oxytocin and Vasopressin in Cardiovascular Regulation

“…V1bR is located mainly in the inner medulla in the kidney. There is evidence that stimulation of renal V1bR can counterbalance the antidiuretic effect of vasopressin mediated by V2R [ 252 ]. It is likely that the counteractive effects of the stimulation of V1bR and V2 receptors by vasopressin may account for the potent natriuretic effect observed after the combined administration of insulin and vasopressin in rats [ 253 ].…”