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Altered expression of renal acid-base transporters in rats with lithium-induced NDI

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  • Department of Anatomy
  • Biomedical Radio Isotope Techniques
Prolonged lithium treatment of humans and rodents often results in hyperchloremic metabolic acidosis. This is thought to be caused by diminished net H+ secretion and/or excessive back-diffusion of acid equivalents. To explore whether lithium treatment is associated with changes in the expression of key renal acid-base transporters, semiquantitative immunoblotting and immunocytochemistry were performed using kidneys from lithium-treated (n = 6) and control (n = 6) rats. Rats treated with lithium for 28 days showed decreased urine pH, whereas no significant differences in blood pH and plasma HCO3- levels were observed. Immunoblot analysis revealed that lithium treatment induced a significant increase in the expression of the H+-ATPase (B1-subunit) in cortex (190 +/- 18%) and inner stripe of the outer medulla (190 +/- 9%), and a dramatic increase in inner medulla (900 +/- 104%) in parallel to an increase in the expression of type 1 anion exchanger (400 +/- 40%). This was confirmed by immunocytochemistry and immunoelectron microscopy, which also revealed increased density of intercalated cells. Moreover, immunoblotting and immunocytochemistry revealed a significant increase in the expression of the type 1 electrogenic Na+-HCO3- cotransporter (NBC) in cortex (200 +/- 23%) and of the electroneutral NBCn1 in inner stripe of the outer medulla (250 +/- 54%). In contrast, there were no changes in the expression of Na+/H+ exchanger-3 or of the Cl-/HCO3- exchanger pendrin. These results demonstrate that the expression of specific renal acid-base transporters is markedly altered in response to long-term lithium treatment. This is likely to represent direct or compensatory effects to increase the capacity for HCO3- reabsorption, NH4+ reabsorption, and proton secretion to prevent the development of systemic metabolic acidosis.
Original languageEnglish
JournalAmerican Journal of Physiology: Renal Physiology
Pages (from-to)F1244-57
Publication statusPublished - 2003

    Research areas

  • Acidosis, Acids, Animals, Anion Exchange Protein 1, Erythrocyte, Antibody Specificity, Blotting, Western, Carrier Proteins, Diabetes Insipidus, Nephrogenic, Hydrogen-Ion Concentration, Immunohistochemistry, Kidney Cortex, Kidney Tubules, Collecting, Lithium, Male, Membrane Transport Proteins, Proton-Translocating ATPases, Rats, Rats, Sprague-Dawley, Sodium-Bicarbonate Symporters, Sodium-Hydrogen Antiporter, Urine

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