Anales RANF

P.98 RENAL PAPILLA EXPRESSES HIGH LEVELS OF THE UDP- GLUCOSE RECEPTOR P2RY14 F. Baalmann 1 , K. Winter 2 , J. Popkova 3 , V. Lede 1 , J. Brendler 2 , A. Butthof 1 , A. Ricken 2 , T. Schöneberg 1 and A. Schulz 1 1 University Leipzig, Medical Faculty, Rudolf-Schönheimer Institute of Biochemistry, Leipzig, Germany; 2 University Leipzig, Medical Faculty, Institute of Anatomy, Leipzig, Germany; 3 University Leipzig, Medical Faculty, Institute of Medical Physics and Biophysics, Leipzig, Germany. Among the metabotropic P2Y receptors, P2RY14 (GPR105) is activated by UDP- sugars. Some physiological relevance of P2RY14 has been shown in the immune system and insulin secretion but its broader expression suggests involvement in additional functions. Using a knockout/knockin reporter (LacZ) mouse model and quantitative real-time PCR we found P2RY14 expression in kidney, most prominent in the renal papilla. General assessment of kidney function revealed no difference between wildtype and knockout mice regarding urine excretion, kidney weight, microscopic morphology and zonation of the kidney. However, immunofluorescence staining for the principal cell marker aquaporin 2 showed colocalization with β -galactosidase expressing cells in our knockout mice. To investigate P2RY14 function in renal papilla at the molecular level, we performed RNA sequencing of wildtype and knockout papillae. It revealed 409 differentially expressed genes. Highest expression differences between WT and KO papillae were found for GPR171 and the serine palmitoyl CoA- transferase small subunit B (Sptssb). GPR171 neighbors P2RY14 on chromosome 3 and may compensate for P2RY14 deficiency. Sptssb is a regulatory subunit of the serine palmitoyl CoA-transferase (SPT). SPT catalyzes the condensation of serine and palmitoyl-CoA which is the first and rate-limiting step in the biosynthesis of sphingolipids. Moreover, expression of additional genes related to sphingolipid metabolism and signaling differed significantly. Analyses of sphingolipid composition of the kidney papilla using thin-layer chromatography and ESI-MS showed a significant decrease in the amount of 16:0 sphingomyelin, a product generated downstream of SPT. Our data suggests that P2RY14 in renal papilla may have protective functions against the concentrated urine and modulates sphingomyelin metabolism.