Interaction and transport of kynurenic acid via human organic anion transporters hOAT1 and hOAT3

Transport of Xanthurenic Acid by Rat/Human Organic Anion Transporters OAT1 and OAT3

“…6,13) The present study confirms that its derivative, xanthurenic acid, is also their substrate. Of the kynurenine pathway metabolites, xanthurenic acid is the second compound that was showed to be transported by OAT1 and OAT3.…”

“…An uptake experiment using Xenopus laevis oocytes was performed as previously reported. 6,13) Briefly, capped RNA encoding each of the various organic anion transporters was transcribed from appropriate restriction enzyme-linearized pBK-CMV containing cDNA of rOAT1, hOAT1, rOAT3, or hOAT3, with T3 RNA polymerase. After 50 nL of water or cRNA (25 ng) was injected into defolliculated oocytes, the oocytes were maintained in modified Barth's medium (88 mM NaCl, 1 mM KCl, 0.33 mM Ca(NO 3 ) 2 , 0.4 mM CaCl 2 , 0.8 mM MgSO 4 , 2.4 mM NaHCO 3 , and 5 mM HEPES, pH 7.4) containing 50 mg/L gentamicin at 18 C. Two days after injection, the uptake reaction was initiated by incubating the oocytes in 500 mL uptake buffer (96 mM NaCl, 2 mM KCl, 1.8 mM CaCl 2 , 1 mM MgCl 2 , and 5 mM HEPES, pH 7.4) with each y To whom correspondence should be addressed.…”

“…Although kynurenic acid amounts have been argued based on findings of the metabolic enzymes in the kynurenine pathway, our laboratory recently reported that human organic anion transporters 1 (hOAT1) and 3 (hOAT3) efficiently transported kynuirenic acid. 6) These transporters are expressed in the basolateral membrane of the renal proximal tubule, and are responsible for tubular uptake of organic anions from the blood. 7,8) In addition, in rats, OAT3 was found to be expressed at the abluminal membrane of brain capillary endothelial cells and to play an important role in the transport of organic anions from brain to blood.…”

Urine 3-hydroxykynurenine is higher during the postovulatory phase than in the preovulatory phase indicating a higher vitamin B6 requirement

“…Organic acids that have not been metabolized are generally excreted into urine. 28) In the liver, the metabolic ability of Trp is much stronger compared with non-hepatic tissues; most of the intermediates can be almost completely metabolized into acetyl-CoA via ACMS although a little part of ACMS is non-enzymatically converted into QA. Thus, the accumulation of intermediates such as AnA, KA, 3-HK, XA, and 3-HA in the liver does not occur.…”

Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid

“…Our laboratory has been interested in transport of bioactive substances by OAT1 and OAT3. Recently, we examined interaction of the metabolites of the kynurenine pathway, a main route for the tryptophan metabolism, with OAT1 and OAT3, and represented that kynurenic acid and xanthurenic acid were transported by them (5,6). Kynurenic acid antagonizes N-methyl D-aspartate (NMDA) receptor in the brain under physiological conditions, and is accepted as the key molecule in several psychiatric disorders (3).…”