Organic anion transporters OAT1 and OAT4 mediate the high affinity transport of glutarate derivatives accumulating in patients with glutaric acidurias.
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Organic anion transporters OAT1 and OAT4 mediate the high affinity transport of glutarate derivatives accumulating in patients with glutaric acidurias. / Hagos, Yohannes; Krick, Wolfgang; Braulke, Thomas; Mühlhausen, Chris; Burckhardt, Gerhard; Burckhardt, Birgitta C.
in: PFLUG ARCH EUR J PHY, Jahrgang 457, Nr. 1, 1, 2008, S. 223-231.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Organic anion transporters OAT1 and OAT4 mediate the high affinity transport of glutarate derivatives accumulating in patients with glutaric acidurias.
AU - Hagos, Yohannes
AU - Krick, Wolfgang
AU - Braulke, Thomas
AU - Mühlhausen, Chris
AU - Burckhardt, Gerhard
AU - Burckhardt, Birgitta C
PY - 2008
Y1 - 2008
N2 - Glutaric acidurias are rare inherited neurodegenerative disorders accompanied by accumulation of the metabolites glutarate (GA) and 3-hydroxyglutarate (3OHGA), glutaconate, L: -, or D: -2-hydroxyglutarate (L: -2OHGA, D: -2OHGA) in all body fluids. Oocytes expressing the human (h) sodium-dicarboxylate cotransporter (NaDC3) showed sodium-dependent inward currents mediated by GA, 3OHGA, L: -, and D: -2OHGA. The organic anion transporters (OATs) were examined as additional transporters for GA derivatives. The uptake of [(3)H]p-aminohippurate in hOAT1-transfected human embryonic kidney (HEK293) cells was inhibited by GA, 3OHGA, D: -, or L: -2OHGA in a concentration-dependent manner. None of these compounds affected the hOAT3-mediated uptake of [(3)H]estrone sulfate (ES). In hOAT4-expressing cells and oocytes, ES uptake was strongly increased by intracellular GA derivatives. The data provide a model for the concerted action of OAT1 and NaDC3 mediating the basolateral uptake, and OAT4 mediating apical secretion of GA derivatives from proximal tubule cells and therefore contribute to the renal clearance of these compounds.
AB - Glutaric acidurias are rare inherited neurodegenerative disorders accompanied by accumulation of the metabolites glutarate (GA) and 3-hydroxyglutarate (3OHGA), glutaconate, L: -, or D: -2-hydroxyglutarate (L: -2OHGA, D: -2OHGA) in all body fluids. Oocytes expressing the human (h) sodium-dicarboxylate cotransporter (NaDC3) showed sodium-dependent inward currents mediated by GA, 3OHGA, L: -, and D: -2OHGA. The organic anion transporters (OATs) were examined as additional transporters for GA derivatives. The uptake of [(3)H]p-aminohippurate in hOAT1-transfected human embryonic kidney (HEK293) cells was inhibited by GA, 3OHGA, D: -, or L: -2OHGA in a concentration-dependent manner. None of these compounds affected the hOAT3-mediated uptake of [(3)H]estrone sulfate (ES). In hOAT4-expressing cells and oocytes, ES uptake was strongly increased by intracellular GA derivatives. The data provide a model for the concerted action of OAT1 and NaDC3 mediating the basolateral uptake, and OAT4 mediating apical secretion of GA derivatives from proximal tubule cells and therefore contribute to the renal clearance of these compounds.
M3 - SCORING: Zeitschriftenaufsatz
VL - 457
SP - 223
EP - 231
JO - PFLUG ARCH EUR J PHY
JF - PFLUG ARCH EUR J PHY
SN - 0031-6768
IS - 1
M1 - 1
ER -
