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Renal Expression of Adhesion GPCR Gpr116 (ADGRF5) Contributes to Urinary Concentration in Mice
Author(s) -
Zaidman Nathan,
Pluznick Jennifer
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.862.35
Subject(s) - g protein coupled receptor , kidney , receptor , urinary system , medicine , endocrinology , hek 293 cells , knockout mouse , chemistry , aquaporin 2 , microbiology and biotechnology , biology , water channel , mechanical engineering , engineering , inlet
G‐protein coupled receptors (GPCR) are a large and diverse family of integral membrane proteins that recognize a tremendous assortment of extracellular molecules including neurotransmitters, hormones, light and odors. They are a common target of pharmaceutical drug development, and uncovering the function of novel GPCRs in the kidney represents a wealth of untapped therapeutic potential. We previously performed an mRNA screen for novel GPCRs in the kidney to identify promising yet overlooked renal GPCRs. This screen revealed that Gpr116, an adhesion‐class GPCR, is highly expressed in the kidney. To understand the role of Gpr116 in renal physiology, we have taken a multidisciplinary approach. Using transfected HEK293 cells expressing cloned Gpr116, we validated a monoclonal antibody for Gpr116. In murine kidney, this antibody localizes Gpr116 to the apical membrane of intercalated cells in the collecting duct of mouse kidneys. This staining is absent in kidneys from targeted knockout (KO) of Gpr116 in renal tubules (Gpr116flox/flox, ksp‐Cre). Additionally, kidney‐specific KO animals have significantly reduced spot urine osmolality (1552±71 mOsm/kg, N=11) compared to wild‐type (WT) (2097±76, N=10, p<0.0001) and heterozygous (2423±86, N=6, p<0.0001) littermates. Furthermore, following 24‐hours of dehydration plasma vasopressin is not significantly upregulated from baseline in KO animals, but is in WT littermates. However, osmolality of 24‐hour urine collections from metabolic cages are not significantly different between the WT and KO groups. Overall, these results suggest a role for Gpr116 in the urinary concentrating mechanisms in the murine kidney. This study establishes a physiologic role of the previously understudied Gpr116 in the murine kidney and demonstrates the scientific potential of future investigations into novel GPCRs. Support or Funding Information Research was funded by NIH F32DK116499 (N.A.Z.) and NIH R01DK107726 (J.L.P.). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .