Kidney Week

Abstract: TH-PO494

Secretin-Stimulated Urinary HCO3- Excretion: A Function of CFTR and Pendrin

Session Information

• Fluid and Electrolytes: Basic - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Berg, Peder, Aarhus University, Aarhus, Denmark

Peder Berg,

• Cabrita, Inês, Physiology, University of Regensburg, Germany, Regensburg, Germany

Inês Cabrita,

• Schreiber, Rainer, University of Regensburg, Regensburg, Germany

Rainer Schreiber,

• Kunzelmann, Karl, University of Regensburg, Regensburg, Germany

Karl Kunzelmann,

• Leipziger, Jens G., Aarhus University, Aarhus, Denmark

Jens G. Leipziger,

Background

The gastro-intestinal hormone secretin (SCT), the first hormone ever discovered (Bayliss and Starling, ca. 1905), is able to acutely increase the amount of HCO₃^- in the urine, but the underlying mechanism remains enigmatic. The actions of secretin are well understood in gastro-intestinal physiology; among many functions it acts as an important activator of pancreatic HCO₃^- secretion. Intriguingly, the SCT receptor is also expressed in the collecting duct (CD) of the kidney.

Methods

Real time monitoring of urine flow and urinary pH was allowed by bladder catheterization and insertion of micro pH-electrodes in the outflow of the catheter in i.v. anaesthetized mice.

Results

Here, we show that SCT elicits acute urinary alkalisation, increases urinary [HCO₃^-] and urinary HCO₃^- excretion rate in anaesthetized mice. This effect is present in multiple mouse strains corroborating data from older studies in healthy humans. Importantly, we identified that the SCT effect is completely absent in mice lacking the apical Cl^-/HCO₃^- exchanger pendrin, which, in the kidney, is exclusively expressed in the apical membrane of β-IC of the CNT/CD. Moreover, we found that the SCT effect on urinary pH is dramatically diminished in mice with either global knock-out of CFTR or renal tubule-specific knock-out of CFTR. The effect on urinary [HCO₃^-] and urinary HCO₃^- excretion is completely abolished in both CF animal models, corroborating early data from children suffering from cystic fibrosis. Noteworthy, CFTR expression has been shown to be several folds higher in β-IC cells compared to α-IC and principal cells.

Conclusion

In conclusion, this study has defined the molecular mechanism of SCT-induced urinary HCO₃^- excretion as a function of the specific activation of the β-IC of the CD. Thus, in close similarity to the established mechanism of SCT-induced HCO₃^- excretion in the exocrine pancreas, an analogous mechanism was identified in the kidney.

Funding

• Government Support - Non-U.S.