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Potential role of purinergic signaling in lithium-induced nephrogenic diabetes insipidus.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2009 May; Vol. 296 (5), pp. F1194-201. Date of Electronic Publication: 2009 Feb 25. - Publication Year :
- 2009
-
Abstract
- Lithium (Li)-induced nephrogenic diabetes insipidus (NDI) has been attributed to the increased production of renal prostaglandin (PG)E(2). Previously we reported that extracellular nucleotides (ATP/UTP), acting through P(2y2) receptor in rat medullary collecting duct (mCD), produce and release PGE(2). Hence we hypothesized that increased production of PGE(2) in Li-induced NDI may be mediated by enhanced purinergic signaling in the mCD. Sprague-Dawley rats were fed either control or Li-added diet for 14 or 21 days. Li feeding resulted in marked polyuria and polydipsia associated with a decrease in aquaporin (AQP)2 protein abundance in inner medulla ( approximately 20% of controls) and a twofold increase in urinary PGE(2). When acutely challenged ex vivo with adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), UTP, or ADP, mCD of Li-fed rats showed significantly higher increases (50-130% over control diet-fed rats) in PGE(2) production, indicating that more than one subtype of P(2y) receptor is involved. This was associated with a 3.4-fold increase in P(2y4), but not P(2y2), receptor mRNA expression in the inner medulla of Li-fed rats compared with control diet-fed rats. Confocal laser immunofluorescence microscopy revealed predominant localization of both P(2y2) and P(2y4) receptors in the mCD of control or Li diet-fed rats. Together, these data indicate that in Li-induced NDI 1) purinergic signaling in the mCD is sensitized with increased production of PGE(2) and 2) P(2y2) and/or P(2y4) receptors may be involved in the enhanced purinergic signaling. Our study also reveals the potential beneficial effects of P(2y) receptor antagonists in the treatment and/or prevention of Li-induced NDI.
- Subjects :
- Animals
Diabetes Insipidus, Nephrogenic chemically induced
Dinoprostone urine
Fluorescent Antibody Technique
Gene Expression physiology
Kidney Medulla metabolism
Kidney Tubules, Collecting metabolism
Lithium toxicity
Male
Polyuria chemically induced
Polyuria metabolism
Polyuria physiopathology
Rats
Rats, Sprague-Dawley
Receptors, Purinergic P2 genetics
Receptors, Purinergic P2Y1
Receptors, Purinergic P2Y2
Signal Transduction drug effects
Diabetes Insipidus, Nephrogenic metabolism
Diabetes Insipidus, Nephrogenic physiopathology
Receptors, Purinergic P2 metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1931-857X
- Volume :
- 296
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 19244398
- Full Text :
- https://doi.org/10.1152/ajprenal.90774.2008