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Abstract: FR-PO603

Effect of Loading NH4Cl in P2Y2 Receptor Knockout and Wild-Type Mice

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Roedel, Marshall R., Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
  • Raphael, Kalani L., Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
  • Liu, Tao, Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
  • Carlson, Noel G., Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
  • Kishore, Bellamkonda K., Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
Background

Chronic lithium (Li) administration for bipolar disorder causes renal tubular acidosis. In animal models, Li invokes collecting duct remodeling (CD-R) resulting in an increased proportion of [H+]-ATPase-positive intercalated cells, presumably to increase kidney H+ excretion. We reported that genetic deletion of P2Y2 receptor blunts this Li-induced CD-R response, suggesting that P2Y2 receptor facilitates H+ elimination in response to an acid load. To investigate the role of P2Y2 receptor in acid-base regulation, we evaluated the effect of NH4Cl loading on blood and urinary acid-base indices in P2Y2 knockout (KO) and wild type (WT) mice.

Methods

Groups of WT or KO mice (B6D2; N=5-6/group) were fed standard rodent chow and given tap water with/without 0.28 M NH4Cl for 9 days and humanely euthanized. Terminal urine and blood samples were collected and analyzed for indices of acid-base homeostasis.

Results

Table shows the terminal data. NH4Cl loading induced a more severe metabolic acidosis in P2Y2 receptor KO than WT mice as evidenced by the markedly lower blood pH, HCO3 and BE, and increased water intake (not shown here). Urinary NH3 excretion was slightly lower in KO than WT mice despite having more severe metabolic acidosis, suggesting that kidney NH3 production or excretion is impaired in KO. The higher than expected pCO2 (expected pCO2 ~ 26 mm Hg) for the degree of metabolic acidosis induced by NH4Cl loading, and the higher pCO2 in KO than WT under basal conditions suggests that P2Y2 receptor may regulate respiratory ventilation.

Conclusion

P2Y2 receptor seems to have an important role in the maintenance of acid-base balance. This may be through facilitating CD-R in response to an acid load and participating in respiratory ventilation.

ParameterWT-CNTKO-CNTWT-NH4ClKO-NH4Cl
Blood pH7.40 ± 0.017.33 ± 0.047.32 ± 0.027.16 ± 0.03*
Blood pCO2 (mm Hg)31.78 ± 1.6841.82 ± 4.37**35.57 ± 4.4834.22 ± 0.62
Blood HCO3 (mEq/L)19.48 ± 0.9720.26 ± 0.9818.23 ± 2.0612.28 ± 0.92*
Blood BE (Base Excess)-5.20 ± 0.86-5.80 ± 0.73-7.67 ± 1.91-16.30 ± 1.41*
Blood Urea Nitrogen (mg/dl)19.68 ± 0.3724.92 ± 1.2127.04 ± 1.0229.12 ± 1.78
Urine NH3 (µmol/day/20 g bw)8.45 ± 1.879.77 ± 1.6282.08 ± 8.19***69.99 ± 12.82***

*significantly different (P < 0.05) from the corresponding value in WT-NH4Cl group; **significantly different (P < 0.05) from the WT-CNT group; ***significantly different from the corresponding control (CNT) groups.

Funding

  • Veterans Affairs Support