Abstract: TH-PO1028

Acute Secretin-Induced Urinary HCO3- Excretion: A Function of Pendrin

Session Information

  • Acid Base: Basic
    November 02, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

  • 701 Acid-Base: Basic

Authors

  • Berg, Peder, Aarhus University, Aarhus, Denmark
  • Larsen, Casper K., Aarhus University, Aarhus, Denmark
  • Cabrita, Inês, Physiology, University of Regensburg, Germany, Regensburg, Germany
  • Kunzelmann, Karl, University of Regensburg, Regensburg, Germany
  • Leipziger, Jens G., Aarhus University, Aarhus, Denmark
Background

The gastro-intestinal hormone secretin is able to acutely increase the amount of HCO3- in the urine by a currently unknown mechanism. The actions of secretin are well understood in gastro-intestinal physiology; among many functions it acts as an important activator of pancreatic HCO3- secretion. The secretin receptor (SCTR) is also expressed in kidney collecting ducts (CD), the function here is not well defined. The present study investigated the acute effects of bolus injections of secretin (i.p., 10µg) on urinary pH in Pendrin knockout (KO) and wildtype (WT) mice.

Methods

Real time monitoring of urine flow and urinary pH was performed by bladder catheterization and insertion of micro pH-electrodes in the outflow of the catheter in i.v. anaesthetized mice. Two different protocols were used to assess the functional effects of secretin on urinary pH:
1. Mice were under a continuous i.v. infusion through a tail vein catheter. After 30 minutes the animals were injected with either secretin or vehicle.
2. After a gavage load, mice were injected with furosemide (0.2µg/g BW, i.p.) and subsequently treated with secretin or vehicle.

Results

1. WT secretin treated animals had a significant transient urinary alkalization, peak difference: 0.41 pH units (n=6, p=0.014), whereas no alkalization was observed in the secretin treated KO mice and neither in sham injected WT and KO mice.
2. WT secretin treated animals had a significant transient urinary alkalization, peak difference: 0.64 pH units (n=6, p=0.002), whereas no alkalization was observed in the secretin treated KO mice and neither in sham injected WT and KO mice.
Furthermore, SCTR mRNA was specifically localized only in isolated connecting tubules and collecting ducts. In IHC results the SCTR (basolateral) co-localized with Pendrin (apical).

Conclusion

Secretin is a potent activator of renal HCO3- excretion. Its mechanism requires functional Pendrin (SLC26A4) and is likely mediated via the SCTR in β-intercalated cells of the collecting duct.

Funding

  • Government Support - Non-U.S.