RGD Reference Report - Renal uptake of substrates for organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2 is altered in rats with adenine-induced chronic renal failure.

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Renal uptake of substrates for organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2 is altered in rats with adenine-induced chronic renal failure.
Authors:	Komazawa, H Yamaguchi, H Hidaka, K Ogura, J Kobayashi, M Iseki, K
Citation:	Komazawa H, etal., J Pharm Sci. 2013 Mar;102(3):1086-94. doi: 10.1002/jps.23433. Epub 2012 Dec 29.
RGD ID:	7243177
Pubmed:	PMID:23280877 (View Abstract at PubMed)
DOI:	DOI:10.1002/jps.23433 (Journal Full-text)
Chronic renal failure (CRF) leads to decreased drug renal clearance and glomerular filtration rate. However, little is known about renal tubular excretion and reabsorption in CRF. We examined transport activity of renal transporters using rats with adenine-induced CRF. We examined the effect of adenine-induced CRF on mRNA level, protein expression of transporters expressed in kidney by real-time polymerase chain reaction, and western blotting. In vivo kidney uptake clearances of benzylpenicillin and metformin, which are typical substrates for renal organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2, respectively, were evaluated. Protein and mRNA expression levels of Oat1, Oat 3, Oct1, and Oct2 were significantly decreased in adenine-induced CRF rats. On the contrary, levels of P-glycoprotein and Mdr1b mRNA were significantly increased in adenine-induced CRF rats. The mRNA expression levels of Oatp4c1, Mate1, Urat1, Octn2, and Pept1 were significantly decreased. Kidney uptake clearance of benzylpenicillin and that of metformin were significantly decreased in adenine-induced CRF rats. Also, serum from CRF rats did not affect Oat1, Oat3, Oct1, and Oct2 function. In conclusion, our results indicate that adenine-induced CRF affects renal tubular handling of drugs, especially substrates of Oat1, Oat3, Oct1, and Oct2.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
SLC22A2	Human	end stage renal disease		ISO	Slc22a2 (Rattus norvegicus)		RGD
Slc22a2	Rat	end stage renal disease		IEP			RGD
Slc22a2	Mouse	end stage renal disease		ISO	Slc22a2 (Rattus norvegicus)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Slc22a2 (solute carrier family 22 member 2)

Genes (Mus musculus)

Slc22a2 (solute carrier family 22 (organic cation transporter), member 2)

Genes (Homo sapiens)

SLC22A2 (solute carrier family 22 member 2)

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Renal uptake of substrates for organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2 is altered in rats with adenine-induced chronic renal failure.