Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI.

@article{Christensen2004ChangesIC,
  title={Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI.},
  author={Birgitte M Christensen and David Marples and Young-Hee Kim and Weidong Wang and J{\o}rgen Fr{\o}kiaer and S{\o}ren Steen Nielsen},
  journal={American journal of physiology. Cell physiology},
  year={2004},
  volume={286 4},
  pages={
          C952-64
        }
}
Lithium treatment for 4 wk caused severe polyuria, dramatic downregulation in aquaporin-2 (AQP-2) expression, and marked decrease in AQP-2 immunoreactivity with the appearance of a large number of cells without AQP-2 labeling in the collecting ducts after lithium treatment. Surprisingly, this was not all due to an increase in AQP-2-negative principal cells, because double immunolabeling revealed that the majority of the AQP-2-negative cells displayed [H(+)]ATPase labeling, which identified them… 
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TLDR
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TLDR
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Lithium reduces aquaporin-2 transcription independent of prostaglandins.
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References

SHOWING 1-10 OF 44 REFERENCES
Altered expression of renal acid-base transporters in rats with lithium-induced NDI.
TLDR
Results demonstrate that the expression of specific renal acid-base transporters is markedly altered in response to long-term lithium treatment, likely to represent direct or compensatory effects to increase the capacity for HCO3- re absorption, NH4+ reabsorption, and proton secretion to prevent the development of systemic metabolic acidosis.
Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla.
TLDR
Lithium causes marked downregulation of AQP2 expression, only partially reversed by cessation of therapy, thirsting or dDAVP treatment, consistent with clinical observations of slow recovery from lithium-induced urinary concentrating defects.
Altered expression of renal AQPs and Na(+) transporters in rats with lithium-induced NDI.
TLDR
Severe downregulation of AQP2 and AQP3 appears to be important for the development of Li-induced polyuria, while the increased or unchanged expression of NHE3, BSC-1, Na-K-ATPase, and TSC indicates that these Na(+) transporters do not participate in the developmentof Li- induced polyuria.
Remodeling the cellular profile of collecting ducts by chronic carbonic anhydrase inhibition.
TLDR
The cellular profile of the collecting ducts of adult rats can be remodeled by inhibiting CA activity in rats by using osmotic pumps containing acetazolamide, suggesting that CA activity plays an important role in determining the differentiated phenotype of medullary collecting duct epithelial cells.
Axial heterogeneity in basolateral AQP2 localization in rat kidney: effect of vasopressin.
TLDR
There was no increase in AQP2 labeling of the BLM in response to short-term dDAVP, and acute V(2)-receptor antagonist treatment did not cause retrieval of AQP 2 from the BLM.
Downregulation of aquaporin-2 parallels changes in renal water excretion in unilateral ureteral obstruction.
TLDR
In bilateral ureteral obstruction, both aquaporin-2 (AQP2) levels and urinary concentrating capacity are markedly reduced, which together with the reduced expression and elevated free water clearance strongly suggests a role of AQP2 in the observed compensatory diuresis from nonobstructed kidneys.
Aquaporin-3 water channel localization and regulation in rat kidney.
TLDR
Investigating the localization and regulation in the kidney of peptide-derived, affinity-purified polyclonal antibody to aquaporin-3 found that the expression of AQP-3 is regulated on a long-term basis, suggesting that this water channel is not regulated acutely through vesicular trafficking.
Vasopressin-elicited water and urea permeabilities are altered in IMCD in hypercalcemic rats.
TLDR
It is concluded that selective alterations in IMCD transport occur in hypercalcemia, permitting the body to dispose of excess calcium without forming calcium-containing renal stones.
Role of apoptotic and nonapoptotic cell death in removal of intercalated cells from developing rat kidney.
TLDR
It is demonstrated that intercalated cells are deleted from the MCD by two distinct mechanisms, one involving apoptosis and subsequent phagocytosis by neighboring principal cells or IMCD cells.
Effect of lithium and amiloride on collecting tubule transport enzymes.
TLDR
The mechanism of action whereby these two agents result in distal renal tubular acidosis in humans and animals are different, and the biochemical differences seen with these drugs may explain the more severe acidemia universally found in animals after chronic Li administration.
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