Kidney Week

Abstract: TH-PO187

Prostaglandin E2 Receptor 4 Contributes to Regulating Epithelial Sodium Channel (ENaC) Activity in the Kidney Collecting Duct

Session Information

• Hypertension and CVD: Basic Research Findings
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Yang, Ting, Duke University, Durham, North Carolina, United States

Ting Yang, MD, PhD

• Pochynyuk, Oleh, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States

Oleh Pochynyuk, PhD

Background

PGE₂ and its EP4 receptor (EP4R) play important role in blood pressure control. Our previous work showed conditional deletion of EP4R from whole kidney epithelia caused exacerbated blood pressure elevation, sodium retention, and increased responsiveness to ENaC inhibitor during Ang II-HTN. Thus, we hypothesize that EP4R resists the development of hypertension through actions in the CD to reduce sodium reabsorption via ENaC.

Methods

We used the patch clamp electrophyhsiology techniques in isolated CD from C57BL/6 mice to characterize the contribution of EP4 to ENaC activity. Additionally, we used an immortalized mouse collecting duct cell line (mpkCCDc14) to investigate the potential contribution of EP4 downstream signaling in regualting ENaC function.

Results

PGE₂ significantly inhibited the P_o of ENaC. This effect was abolished by EP4R antagonist (L161,982, Fig. 1). Using the mpkCCDc14 cells, we found that EP4 silencing using siRNA significantly inhibited the PGE₂ (10mM, 10min) induced phosphorylation of p-44/42 MAPK/ERK (Fig. 2).

Conclusion

Our results indicate that PGE₂ directly inhibits the kidney collecting duct ENaC channel open probability via EP4 receptor. The phosphorylation of MAPK/ERK pathway may contribute to teh ENaC regulation mediated by PGE2-EP4 signaling.

Funding

• NIDDK Support