RGD Reference Report - Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney. - Rat Genome Database

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Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney.

Authors: Ohta, KY  Inoue, K  Hayashi, Y  Yuasa, H 
Citation: Ohta KY, etal., Drug Metab Dispos. 2006 Nov;34(11):1868-74. Epub 2006 Aug 23.
RGD ID: 2316962
Pubmed: PMID:16928787   (View Abstract at PubMed)
DOI: DOI:10.1124/dmd.106.010876   (Journal Full-text)

We have cloned and functionally characterized the rat ortholog of multidrug and toxin extrusion type transporter 1 (rMATE1). The mRNA of rMATE1 was strongly expressed in kidney and detectable in the various tissues such as brain, stomach, colon, lung, liver, spleen, skeletal muscle, and prostate. When stably expressed in HEK293 cells, rMATE1 could mediate the transport of tetraethylammonium (TEA) and cimetidine under the condition where the membrane potential was disrupted by a high concentration of potassium ion and intracellular pH was reduced by NH(4)Cl pretreatment. When extracellular pH was changed from 5.5 to 8.5, the transport of TEA by rMATE1 was greatest at pH 7.5. Kinetic analyses showed that the transports of TEA and cimetidine mediated by rMATE1 were both saturable with a K(m) of 260 +/- 10 and 3.01 +/- 0.21 muM, respectively. It was found that cimetidine is the most potent inhibitor of rMATE1, and many other organic cations, such as 1-methyl-4-phenylpyridinium, amiloride, imipramine, and quinidine, are also effective as inhibitors. Pretreatment of the cells expressing rMATE1 with p-chloromercuribenzene sulfonate significantly reduced TEA transport, but this effect was totally reversed by subsequent treatment with dithiothreitol. These results indicate that the functional nature of rMATE1 is consistent with that of the hypothetical organic cation/H(+) antiporter system in the brush-border membrane of the renal tubular epithelial cells. Accordingly, these results suggest that rMATE1 is an electroneutral and multispecific organic cation transporter energized by the trans-proton gradient, and plays a physiological role in renal secretion of organic cations, including clinically used cationic drugs.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension MODEL: spontaneousIAGP 2316962compared to LL/MavRGD 
hypertension MODEL: spontaneousIAGP 2316962compared with WKYRGD 
Left Ventricular Hypertrophy MODEL: spontaneousIAGP 2316962compared to LL/MavRGD 
Left Ventricular Hypertrophy MODEL: spontaneousIAGP 2316962compared with WKYRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
monoatomic cation transmembrane transport  IDA 2316962cimetidineRGD 
organic cation transport  IDA 2316962 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
amide transmembrane transporter activity  IDA 2316962fluoroquinolonesRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased systemic arterial systolic blood pressure  IAGP 2316962compared to LN/MavRGD 
increased systemic arterial systolic blood pressure  IAGP 2316962compared with WKYRGD 
Objects Annotated

Genes (Rattus norvegicus)
Slc47a1  (solute carrier family 47 member 1)

Strains
LH/Mav  (NA)
SHR  (Spontaneously Hypertensive Rat)

Objects referenced in this article
Strain LH/MavRrrc Lyon Hypertensive Rattus norvegicus
Strain SD-Tg(Ren2)27 null Rattus norvegicus

Additional Information