Human organic anion transporter hOAT3 is a potent transporter of cephalosporin antibiotics, in comparison with hOAT1.

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Ueo H, Motohashi H, Katsura T, Inui K

Human organic anion transporter hOAT3 is a potent transporter of cephalosporin antibiotics, in comparison with hOAT1.

Biochem Pharmacol. 2005 Oct 1;70(7):1104-13. doi: 10.1016/j.bcp.2005.06.024.

PubMed ID

16098483 [ View in PubMed

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Abstract

We examined the substrate specificity of human organic anion transporter (hOAT) 1 and hOAT3 for various cephalosporin antibiotics, cephaloridine, cefdinir, cefotiam, ceftibuten, cefaclor, ceftizoxime, cefoselis and cefazolin by using HEK293 cells stably transfected with hOAT1 or hOAT3 cDNA (HEK-hOAT1, HEK-hOAT3). Additionally, we examined the uptake of various compounds by these transfectants. The mRNA level of hOAT3 in HEK-hOAT3 was about three-fold that of hOAT1 in HEK-hOAT1. Functional expression of hOAT1 and hOAT3 was confirmed by the uptake of p-[14C]aminohippurate and [3H]estrone sulfate, respectively. p-[14C]Aminohippurate, [3H]estrone sulfate, [14C]captopril, [3H]methotrexate, [3H]ochratoxin A, [3H]leucovorin and [3H]cimetidine were shown to be substrates for hOAT1 and hOAT3, and [3H]dehydroepiandrosterone sulfate was shown to be a substrate for hOAT3. All cephalosporin anitibiotics tested were shown to inhibit the uptake of p-[14C]aminohippurate and [3H]estrone sulfate via hOAT1 and hOAT3, respectively, in a dose-dependent manner, and the IC50 values of these antibiotics, except for cefaclor, for the hOAT1-mediated uptake of p-[14C]aminohippurate were within four-fold of those for the hOAT3-mediated uptake of [3H]estrone sulfate. The uptake of cephaloridine, cefdinir and cefotiam by HEK-hOAT3 was 35-50-fold greater than that by control cells. Moreover, the accumulation of the other cephalolsporin antibiotics was significantly greater in HEK-hOAT3 than in control cells. In contrast, the uptake of these antibiotics by HEK-hOAT1 was within two-fold of that by control cells. In conclusion, hOAT3 plays a more important role than hOAT1 in the renal secretion of cephalosporin antibiotics.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Cefdinir	Solute carrier family 22 member 8	Protein	Humans	Unknown	Substrate	Details