期刊
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
卷 26, 期 5, 页码 426-433出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MNH.0000000000000353
关键词
alpha-ketoglutarate; NaCl reabsorption; Oxgr1; pendrin; volume contraction
资金
- National Institutes of Diabetes and Digestive and Kidney Disease [RO1 DK63049, DK54231, DK093501]
- National Kidney Foundation of Maryland Scientific Development
Purpose of review This review describes the recent discoveries about a powerful electroneutral NaCl reabsorption mechanism in intercalated cells, and its regulation by an intrarenal metabolite paracrine, alpha-ketoglutartate, and the G-protein coupled receptor, Oxgr1. Recent findings The distal nephron fine-tunes sodium, chloride, potassium, hydrogen, bicarbonate and water transport to maintain electrolyte homeostasis and blood pressure. Intercalated cells have been traditionally viewed as the professional regulators of acid-base balance, but recent studies reveal that a specific population of intercalated cells, identified by the pendrin-transporter, have a surprising role in the regulation of salt balance. The pendrin-positive intercalated cells (PP-ICs) facilitate electroneutral NaCl reabsorption through the cooperative activation of multitransport protein network. alpha-Ketoglutartate is synthesized and secreted into the proximal tubule lumen in the combined state of metabolic alkalosis and intravascular volume contraction to activate Oxgr1 in PP-IC, which in turn activates the multitransport protein network to drive salt reabsorption and bicarbonate secretion by these cells. Summary Recent studies identify a novel salt transport pathway in intercalated cells that is activated by an intrarenal paracrine system, a-ketoglutartate/Oxgr1. Activation of the paracrine system and transport pathway, particularly during alkalosis and volume contraction, mitigates deleterious salt wasting while restoring acid-base balance.
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