Abstract 141: G-Protein Coupled Receptors GPR37 and GPR37L1 Regulate Sodium Reabsorption in Renal Proximal Tubule Cells
GPR37 and GPR37L1 are closely related G-protein coupled receptors that are expressed mainly in brain glial cells and muscle-myenteric nerve layers in the GI tract. GPR37L1 transgenic mice have decreased systolic blood pressure (SBP) whereas GPR37L1 KO mice have increased SBP. However, there are no studies reporting kidney expression of GPR37 or GPR37L1 or their role in renal blood pressure regulation. Immunostaining and immunoblotting showed that GPR37 and GPR37L1 are expressed in the apical membrane of proximal tubules of the mouse kidney; RT-PCR on proximal tubule and collecting duct cells obtained by laser capture micro-dissection of mouse kidney sections, confirmed these findings. In addition, chronic high salt diet increased the renal expression of prosaposin, a precursor for saposin C, a natural ligand for GPR37 and GPR37L1. Infusion of prosaptide, a synthetic ligand for GPR37 and GPR37L1, decreased SBP in mice by 10 mm Hg. To determine the roles of GPR37 and GPR37L1 in renal Na+ transport, we over-expressed separately the two proteins in human renal proximal tubule (RPT) cells (n=3). Intracellular Na+ was increased in GPR37- or GPR37L1-transfected RPT cells (3.1 ± 0.8 and 3.2 ± 0.6 fold respectively, P<0.001) compared with mock-transfected cells. Immunoblot analyses showed increased phosphorylation of Erk1/2 (1.33 ± 0.03 and 1.52 ± 0.06 fold, P<0.05), and ribosomal S6 protein (1.29 ± 0.03.5 and 1.39 ± 0.08 fold, P<0.01) in RPT cells over-expressing GPR37 or GPR37L1, respectively. Na+,K+-ATPase expression was decreased by 29% ± 3.5 (P<0.05) in GPR37L1 transfected RPT cells, but was unaltered in GPR37 transfected RPT cells. Taken together, these results show that both GPR37 and GPR37L1 are expressed in RPT cells and signal via the Erk1/2 pathway. GPR37L1 increases intracellular Na+ in RPT cells by decreasing the exit of Na+ due to a decrease in Na+,K+-ATPase expression and activity at the basolateral membrane while GPR37 increases intracellular Na+, by a mechanism independent of Na+,K+-ATPase. These results indicate that GPR37 and GPR37L1 may play a role in Na+ reabsorption in RPT cells and may be novel targets to designing drugs to treat patients with hypertension.
Author Disclosures: X. Zheng: None. I. Armando: None. P.A. Jose: None. P. Konkalmatt: None.
- © 2015 by American Heart Association, Inc.