Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla - PubMed (original) (raw)

Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla

D Marples et al. J Clin Invest. 1995 Apr.

Abstract

Lithium, a widely used treatment for bipolar affective disorders, often causes nephrogenic diabetes insipidus. The effect of chronic lithium therapy on the expression of the vasopressin-regulated water channel Aquaporin-2 (AQP2) in rat kidney was examined. Membranes were prepared from inner medulla of one kidney from each rat, while the contralateral one was fixed for immunofluorescence and immunoelectronmicroscopy. Immunoblotting revealed that lithium treatment reduced AQP2 expression dramatically, to 31 +/- 8% after 10 d and to 4 +/- 1% after 25 d, coincident with development of severe polyuria. Immunofluorescence and immunogold quantitation confirmed the lithium-induced decrease in AQP2 expression (from 11.2 +/- 1.0 to 1.1 +/- 0.2 particles/microns 2). The downregulation was only partly reversed by return to lithium-free diet for 1 wk (40 +/- 8% of control). Furthermore, immunoblotting and immunogold quantitation revealed that 2 d of thirsting or 7 d of dDAVP treatment, in the continued presence of lithium, increased AQP2 expression by six- and threefold, respectively, coincident with increased urinary osmolality. Thirsting increased AQP2 immunolabeling mainly of vesicles, whereas dDAVP caused accumulation of AQP2 predominantly in the subapical region and plasma membrane. Thus, 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.

PubMed Disclaimer

Cited by

Molecular mechanisms and therapeutic potential of lithium in Alzheimer's disease: repurposing an old class of drugs.
Shen Y, Zhao M, Zhao P, Meng L, Zhang Y, Zhang G, Taishi Y, Sun L. Shen Y, et al. Front Pharmacol. 2024 Jul 11;15:1408462. doi: 10.3389/fphar.2024.1408462. eCollection 2024. Front Pharmacol. 2024. PMID: 39055498 Free PMC article. Review.
Urinary Extracellular Vesicle Protein Profiling and Endogenous Lithium Clearance Support Excessive Renal Sodium Wasting and Water Reabsorption in Thiazide-Induced Hyponatremia.
Channavajjhala SK, Bramley R, Peltz T, Oosthuyzen W, Jia W, Kinnear S, Sampson B, Martin N, Hall IP, Bailey MA, Dear JW, Glover M. Channavajjhala SK, et al. Kidney Int Rep. 2018 Sep 22;4(1):139-147. doi: 10.1016/j.ekir.2018.09.011. eCollection 2019 Jan. Kidney Int Rep. 2018. PMID: 30596177 Free PMC article.
Drug-induced diabetes insipidus: incidence, prevention and management.
Bendz H, Aurell M. Bendz H, et al. Drug Saf. 1999 Dec;21(6):449-56. doi: 10.2165/00002018-199921060-00002. Drug Saf. 1999. PMID: 10612269 Review.
Aquaglyceroporins in Human Breast Cancer.
Kirkegaard T, Riishede A, Tramm T, Nejsum LN. Kirkegaard T, et al. Cells. 2023 Aug 31;12(17):2185. doi: 10.3390/cells12172185. Cells. 2023. PMID: 37681917 Free PMC article.
Lithium in kidney diseases: big roles for the smallest metal.
Livingston MJ, Dong Z. Livingston MJ, et al. J Am Soc Nephrol. 2014 Mar;25(3):421-3. doi: 10.1681/ASN.2013111216. Epub 2014 Jan 9. J Am Soc Nephrol. 2014. PMID: 24408870 Free PMC article. No abstract available.

References

1. J Biol Chem. 1994 Apr 22;269(16):11993-2000 - PubMed
1. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8984-8 - PubMed
1. Kidney Int Suppl. 1993 Jul;42:S93-8 - PubMed
1. J Clin Invest. 1994 Mar;93(3):1250-6 - PubMed
1. Am J Physiol. 1991 Sep;261(3 Pt 2):F554-66 - PubMed

Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla - PubMed (original) (raw)