Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells.
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Publication year
2009Source
Kidney International. Supplement, 76, 12, (2009), pp. 1258-67ISSN
Publication type
Article / Letter to editor
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Organization
Physiology
Journal title
Kidney International. Supplement
Volume
vol. 76
Issue
iss. 12
Page start
p. 1258
Page end
p. 67
Subject
IGMD 9: Renal disorder; NCMLS 5: Membrane transport and intracellular motilityAbstract
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.
This item appears in the following Collection(s)
- Academic publications [238586]
- Electronic publications [122827]
- Faculty of Medical Sciences [90409]
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