Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is located in the luminal membrane of macula densa cells of the juxtaglomerular apparatus in close proximity to renin-producing granular cells, the cortical thick ascending limb, and cortical and inner medullary collecting duct cells. In order to study its signaling, SUCNR1 was stably expressed in Madin-Darby Canine Kidney (MDCK) cells, where it localized to the apical membrane. Activation of the cells by succinate caused Gq and Gi-mediated intracellular calcium mobilization, transient phosphorylation of extracellular regulated kinase (ERK)1/2 and the release of arachidonic acid along with prostaglandins E2 and I2. Signaling was desensitized without receptor internalization but rapidly resensitized upon succinate removal. Immunohistochemical evidence of phosphorylated ERK1/2 was found in cortical collecting duct cells of wild type but not SUCNR1 knockout streptozotocin-induced diabetic mice, indicating in vivo relevance. Since urinary succinate concentrations in health and disease are in the activation range of the SUCNR1, this receptor can sense succinate in the luminal fluid. Our study suggests that changes in the luminal succinate concentration may regulate several aspects of renal function.
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PMID:Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells. 1977 18

Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease. A classic hallmark of diabetes pathology is the activation of the intrarenal renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation has been elusive. Recently, we described the intrarenal localization of the novel metabolic receptor GPR91 and established some of its functions in diabetes. These include the triggering of renin release in early diabetes via both vascular (endothelial) and tubular (macula densa) sites in the juxtaglomerular apparatus as well as the activation of MAP kinases in the distal nephron-collecting duct, which are important signaling mechanisms in diabetic nephropathy (DN) and renal fibrosis. GPR91 is a cell surface receptor for succinate and during the past few years it has provided a new paradigm for the mechanism of cell stress response in many organs. Beyond its traditional role in the tricarboxylic acid cycle, succinate now has an unexpected hormone-like signaling function, which may provide a feedback between local tissue metabolism, mitochondrial stress, and organ functions. Succinate accumulation in the local tissue environment and GPR91 signaling appear to be important early mechanisms by which cells detect and respond to hyperglycemia and trigger tissue injury in DN. Also, the distal nephron-collecting duct system, which is the major source of (pro)renin in diabetes and has the highest level of GPR91 expression in the kidney, may have an important, active, and early role in the pathogenesis of DN in contrast to the existing glomerulus-centric paradigm.
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PMID:High glucose and renin release: the role of succinate and GPR91. 2086 27