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Abstract: PO1404

P2Y2 Receptor Directly Mediates Collecting Duct Remodeling Induced by Acid Loading in Mice

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

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

Authors

  • Roedel, Marshall R., University of Utah Health, Salt Lake City, Utah, United States
  • Raphael, Kalani L., University of Utah Health, Salt Lake City, Utah, United States
  • Izuhara, Audrey, University of Southern California, Los Angeles, California, United States
  • Kishore, Bellamkonda K., University of Utah Health, Salt Lake City, Utah, United States
  • Peti-Peterdi, Janos, University of Southern California, Los Angeles, California, United States
Background

Previously we reported that genetic deletion of P2Y2-R suppresses lithium(Li)-induced collecting duct (CD) remodeling. Since genetic deletion of P2Y2-R has a generalized ameliorating effect on Li-induced diabetes insipidus, here we evaluated the direct effect of P2Y2-R in CD remodeling using a model of acid loading.

Methods

Groups of WT or P2Y2-R knockout (KO) mice (B6D2; N = 3 or 4/group) were fed standard rodent chow and given tap water with/without addition of 0.28 M NH4Cl for 9 days and humanely euthanized. AQP2 and [H+]-ATPase double immunolabeling was used to identity the principal (PC) and intercalated (IC) cells of the medullary CD, respectively.

Results

As reported previously, KO mice developed more severe metabolic acidosis than WT after NH4Cl loading (not shown here). Furthermore, as shown in the pie charts, statistical analysis of the numbers of cells found a marked increase in the number of medullary ICs in NH4Cl-treated vs. untreated control (CT) mice in WT (28 ± 2 vs. 6 ± 1), but only a blunted response in P2Y2 KO mice (10 ± 1 vs. 4 ± 1, P < 0.001 WT vs. KO). These increases in ICs were associated with significant decreases in the proportion of PC cells in NH4Cl-treated vs. untreated CT mice in WT (72 ± 2 vs. 94 ± 1), and again a blunted response in P2Y2 KO mice (90 ± 1 vs. 96 ± 1, P < 0.001 WT vs. KO).

Conclusion

The data clearly show that P2Y2 receptor has a “direct effect” on CD remodeling in the kidney following acid-loading.

Funding

  • NIDDK Support