Kidney Week

Abstract: FR-PO598

Secretin Activates Pendrin-Dependent HCO₃^- Secretion in β-Intercalated Cells

Session Information

• Fluid and Electrolytes: Basic - I
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Svendsen, Samuel L.C., Aarhus University, Aarhus C, Denmark

Samuel L.C. Svendsen,

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

Jens G. Leipziger,

Background

The secretin receptor is expressed in the intercalated cells (IC) of the collecting duct. Using in vivo mice experiments, we have recently shown that secretin triggers a pronounced and rapid increase of urinary HCO₃^- excretion. Importantly, this secretin effect was completely absent in pendrin (SLC26A4) KO mice and strongly reduced in CFTR KO mice. We hypothesize that secretin directly activates β-intercalated cells (β-IC) of the collecting duct (CD) via stimulation of basolateral secretin receptors.

Methods

We used isolated perfused cortical collecting ducts and intracellular pH measurements in β-ICs to quantify the transport rate of pendrin upon fast removal of luminal chloride in the presence of 24 mM luminal HCO₃^-. Tubules were loaded with the pH indicator dye BCECF-AM from the luminal side to achieve selective IC dye loading. The experiments were done in WT and CFTR KO mice. The initial alkalization rate (ΔpH/Δt) upon luminal chloride removal was taken as measure of pendrin activity in β-ICs. Secretin (10 nM) was applied for 10 min to the basolateral side. Analysis was performed in a strictly paired fashion in the single β-IC before and after secretin and this was compared to time controls with no secretin stimulation.

Results

Mean ΔpH/Δt was markedly increased with secretin (0.20±0.038 pH/min vs. 0.43±0.044 pH/min (24 cells, 4 CDs, 4 mice), p<0.0001). This increase was significantly different from time controls without secretin (p=0.0022, 20 cells, 4 CDs, 4 mice).

Conclusion

These results show that basolateral secretin directly activates pendrin-dependent HCO₃^-secretion in β-ICs. Importantly, HCO₃^- secretion in β-IC is markedly reduced in CFTR KO mice. Thus, our previously demonstrated in vivo effects of secretin align well with those reported here in the isolated perfused CD. This shows that secretin triggers urinary HCO₃^- excretion by activating the β-ICs.

Funding

• Government Support - Non-U.S.