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

Although vasopressin V receptor (VR) mRNA has been detected in the kidney, the precise renal localization as well as pharmacological and physiological properties of this receptor remain unknown. Using the selective V agonist d[Leu, Lys]VP, either fluorescent or radioactive, we showed that VR is mainly present in principal cells of the inner medullary collecting duct (IMCD) in the male rat kidney. Protein and mRNA expression of VR were very low compared with the V receptor (VR). On the microdissected IMCD, d[Leu, Lys]VP had no effect on cAMP production but induced a dose-dependent and saturable intracellular Ca concentration increase mobilization with an EC value in the nanomolar range. This effect involved both intracellular Ca mobilization and extracellular Ca influx. The selective V antagonist SSR149415 strongly reduced the ability of vasopressin to increase intracellular Ca concentration but also cAMP, suggesting a cooperation between VR and VR in IMCD cells expressing both receptors. This cooperation arises from a cross talk between second messenger cascade involving PKC rather than receptor heterodimerization, as supported by potentiation of arginine vasopressin-stimulated cAMP production in human embryonic kidney-293 cells coexpressing the two receptor isoforms and negative results obtained by bioluminescence resonance energy transfer experiments. In vivo, only acute administration of high doses of V agonist triggered significant diuretic effects, in contrast with injection of selective V agonist. This study brings new data on the localization and signaling pathways of VR in the kidney, highlights a cross talk between VR and VR in the IMCD, and suggests that VR may counterbalance in some pathophysiological conditions the antidiuretic effect triggered by VR activation. Although VR mRNA has been detected in the kidney, the precise renal localization as well as pharmacological and physiological properties of this receptor remain unknown. Using original pharmaceutical tools, this study brings new data on the localization and signaling pathways of VR, highlights a cross talk between VR and V receptor (VR) in the inner medullary collecting duct, and suggests that VR may counterbalance in some pathophysiological conditions the antidiuretic effect triggered by VR activation.