engleski

Presence of murine organic anion transporter 1 (mOAT1) in kidneys and brain and interaction with tryptophan metabolites

Organic anion transporters (OATs) facilitate the renal secretion of weak organic acids including endogenous metabolites and drugs. Besides acidic metabolites of neural transmitters, neuroactive tryptophan metabolites like kynurenate (KINA), 3-hydroxykynurenine (3-HK) and quinolinate (QUIN) are postulated to be excreted via a probenecid-sensitive transport system. Immunohystochemical analyses in mouse kidneys revealed the localization of mouse OAT1 (mOAT1) in proximal convoluted tubules. Examinations of mouse brain sectionsshowed positive staining of control neurons. Additionally, we investigated the interaction of mOAT1 with several tryptophan metabolites. We transiently transfected COS 7 cells with mOAT1 and measured the influence of tryptophan metabolites on /H3/PAH uptake. 1 mM of probenecid, KYNA, 3-HK, 5-hydroxyindolate (5-HIAA) and anthranilate (ANTRA) decreased pAT uptake by 50-85%, demonstrating that all these compounds bint to OAT1. 1 mM QUIN showed only a slight, but significant inhibition of PAH uptake. Preloading the cells with 1 mM glutarate, KYNA, 3-HK, 5-HIAA, ANTRA, or QUIN revealed a substantial trans-stimulation of PAH uptake by glutarate, and a significant effect for 5-HIAA, indicating that this compound is translocated by OAT1.

immunocytochemistry; renal secretion

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