Down-regulation of urea transporters in the renal inner medulla of lithium-fed rats.
BACKGROUND
Lithium is commonly used to treat bipolar psychiatric disorders but can cause reduced urine concentrating ability.


METHODS
To test whether lithium alters UT-A1 or UT-B urea transporter protein abundance or UT-A1 phosphorylation, rats were fed a standard diet supplemented with LiCl for 10 or 25 days, and then compared to pair-fed control rats. To investigate another potential mechanism for decreased urea transport, inner medullary collecting duct (IMCD) suspensions from lithium-fed or control rats were incubated with 32P-orthophosphate to measure the phosphorylation of UT-A1.


RESULTS
In lithium-fed rats (25 days), UT-A1 abundance was reduced to 50% of control rats in IM tip and to 25% in IM base, and UT-B abundance was reduced to 40% in IM base. Aquaporin-2 (AQP2) protein abundance was reduced in both IM regions. Vasopressin (100 pmol/L) increased UT-A1 phosphorylation in IMCD suspensions from control but not from lithium-fed rats; a higher vasopressin concentration (100 nmol/L) increased UT-A1 phosphorylation in control and lithium-fed rats.


CONCLUSIONS
Decreases in UT-A1, UT-B, and AQP2 protein abundance, and/or vasopressin-stimulated phosphorylation of UT-A1, can contribute to the reduced urine concentrating ability that occurs in lithium-treated rats.
Klein
Janet D
JD
Renal Division, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA, USA.
Gunn
Robert B
RB
Roberts
Brian R
BR
Sands
Jeff M
JM
D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D004032:Diet; D015536:Down-Regulation; D007679:Kidney Medulla / Q000378:metabolism*; D018021:Lithium Chloride / Q000008:administration & dosage* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000096982:Urea Transporters
D018692:Antimanic Agents; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D002352:Carrier Proteins; D018021:Lithium Chloride; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D000096982:Urea Transporters; C496025:Aqp2 protein, rat