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Abstract: FR-OR28

Extracellular Calcium-Sensing Receptor (CaSR) and Vasopressin Type 2 Receptor (V2R) Interaction: An Emerging Mechanism to Fine-Tune Water Permeability in Renal Cells

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Ranieri, Marianna, Universita degli Studi di Bari Aldo Moro, Bari, Italy
  • Wang, Yanhua, Emory University, Atlanta, Georgia, United States
  • Pierri, Ciro Leonardo, Universita degli Studi di Bari Aldo Moro, Bari, Italy
  • Angelini, Ines, Universita degli Studi di Bari Aldo Moro, Bari, Italy
  • Di Mise, Annarita, Universita degli Studi di Bari Aldo Moro, Bari, Italy
  • Sands, Jeff M., Emory University, Atlanta, Georgia, United States
  • Tamma, Grazia, Universita degli Studi di Bari Aldo Moro, Bari, Italy
  • Valenti, Giovanna, Universita degli Studi di Bari Aldo Moro, Bari, Italy
Background

We have previously shown that Extracellular Calcium-Sensing Receptor (CaSR) signaling counteracts Vasopressin type 2 Receptor (V2R) signaling in renal collecting duct cells. In collecting duct principal cells, the V2R is expressed in both the basolateral and apical membranes.

Methods

Biochemical, computational, and functional methods were used to provide evidence that CaSR and V2R interact as multimeric complex. AQP2-mediated osmotic water permeability measurements were performed to evaluate the functional CaSR/V2R interaction.

Results

In collecting duct MDC4 cells and mouse kidney, immunolocalization and confocal xz reconstruction confirmed that both the CaSR and V2R are co-expressed in the apical membrane with a significant degree of co-localization. Moreover, the CaSR co-immunoprecipitated with the V2R, and stimulation with vasopressin increased the amount of immunoprecipitated CaSR. Proximity ligation experiments confirmed CaSR/V2R interaction and their sensitivity to vasopressin stimulation. In silico comparative modeling analysis allowed us to predict a possible
structure of the CaSR/V2R protein complex. Functional data obtained in isolated perfused rat inner medullary collecting duct indicated that luminal vasopressin acts as a negative feedback system to the basolateral action of vasopressin on osmotic water permeability (Pf), and luminal CaSR activation further inhibited the Pf providing a functional significance to the described receptor-receptor interaction.

Conclusion

This study opens new perspectives on the regulation of AQP2 trafficking and function not considered when the two GPCRs are viewed individually.

Funding

  • Government Support – Non-U.S.