Adhesion-GPCR Gpr116 (ADGRF5) expression inhibits renal acid secretion
Nathan A. Zaidman, Viktor Tomilin, Naghmeh Hassanzadeh Khayyat, Mahendra Damarla, Josephine Tidmore, Diane E. Capen, Dennis Brown, Oleh Pochynyuk, Jennifer L. Pluznick
Abstract
compared to WT littermates. Additionally, immunogold electron microscopy shows a greater accumulation of V-ATPase proton pumps at the apical surface of A-ICs in KO mice compared to controls. Furthermore, pretreatment of split-open collecting ducts with the synthetic agonist peptide significantly inhibits proton flux in ICs. These data suggest a tonic inhibitory role for Gpr116 in the regulation of V-ATPase trafficking and urinary acidification. Thus, the absence of Gpr116 results in a primary excretion of acid in KO mouse urine, leading to mild metabolic alkalosis ("renal tubular alkalosis"). In conclusion, we have uncovered a significant role for Gpr116 in kidney physiology, which may further inform studies in other organ systems that express this GPCR, such as the lung, testes, and small intestine.