Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes.
Approximately 80% of the filtered load of HCO3- is reabsorbed in the proximal tubule via a process of active acid secretion by the luminal membrane. The major mechanism for the transport of HCO3- across the basolateral membrane is via the electrogenic Na+:3HCO3- cotransporter (NBC). Recent molecular cloning experiments have identified the existence of three NBC isoforms (NBC-1, NBC-2, and NBC-3).1 Functional and molecular studies indicate the presence of all three NBC isoforms in the kidney. All are presumed to mediate the cotransport of Na+ and HCO3- under normal conditions and may be functionally altered in certain pathophysiologic states. Specifically, NBC-1 may be up-regulated in metabolic acidosis and potassium depletion and in response to glucocorticoid excess and may be down-regulated in response to HCO3- loading or alkalosis. Recent studies provide molecular evidence indicating the expression of NBC-1 in pancreatic duct cells. NBC is activated by cystic fibrosis transmembrane conductance regulator (CFTR) and plays an important role in HCO3- secretion in the agonist-stimulated state in pancreatic duct cells. The purpose of this review is to summarize recent functional and molecular studies on the regulation of NBCs in physiologic and pathophysiologic states. Possible signals responsible for the regulation of NBCs in these conditions are examined. Furthermore, the possible role of this transporter in acid-base disorders (such as proximal renal tubular acidosis) is discussed.
Soleimani
M
M
Department of Medicine, University of Cincinnati, and the Veterans Affairs Medical Center, Cincinnati, Ohio 45267-0585, USA. Manoocher.Soleimani@uc.edu
Burnham
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CE
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D027982:Sodium-Bicarbonate Symporters
D002352:Carrier Proteins; D027982:Sodium-Bicarbonate Symporters