A5024278208- Drug Transport and Resistance Mechanisms
- Amino Acid Enzymes and Metabolism
- Ion Transport and Channel Regulation
- Pharmacological Effects and Toxicity Studies
- Folate and B Vitamins Research
- Diet and metabolism studies
- Metabolism and Genetic Disorders
- Gastrointestinal motility and disorders
- Adenosine and Purinergic Signaling
- Drug Solubulity and Delivery Systems
- Advanced Drug Delivery Systems
- Antibiotics Pharmacokinetics and Efficacy
- Glycosylation and Glycoproteins Research
- Gout, Hyperuricemia, Uric Acid
- Biochemical Analysis and Sensing Techniques
- Diabetes Treatment and Management
- Monoclonal and Polyclonal Antibodies Research
- Alcoholism and Thiamine Deficiency
- Gastroesophageal reflux and treatments
- Pharmacogenetics and Drug Metabolism
- Biochemical and Molecular Research
- Nitric Oxide and Endothelin Effects
- bioluminescence and chemiluminescence research
- Metabolomics and Mass Spectrometry Studies
- HER2/EGFR in Cancer Research
Tokyo University of Pharmacy and Life Sciences
2016-2025
Nagoya City University
2005-2016
Kinjo Gakuin University
2016
The University of Tokyo
2010
Tokyo Women's Medical University
2010
Okayama University
2010
Kao Corporation (Japan)
2008
Augusta University
2002-2004
Kumamoto University
1998-2000
Kansai Medical University
1996
A microdose study of metformin was conducted to investigate the predictability drug–drug interactions at therapeutic dose (ThD). Healthy subjects received a (100 µg) or ThD (250 mg) orally, with without potent and competitive multidrug toxin extrusion (MATE) inhibitor, pyrimethamine (50 mg, p.o.), in crossover fashion. Pyrimethamine significantly reduced renal clearance by 23 35% ThD, respectively. At but not microdose, it caused significant increases maximum concentration (Cmax) area under...
Cimetidine, an H<sub>2</sub> receptor antagonist, has been used to investigate the tubular secretion of organic cations in human kidney. We report a systematic comprehensive analysis inhibition potency cimetidine for influx and efflux transporters [human cation transporter 1 (hOCT1) hOCT2 multidrug toxin extrusion (hMATE1) hMATE2-K, respectively]. Inhibition constants (<i>K</i><sub>i</sub>) were determined by using five substrates [tetraethylammonium (TEA), metformin,...
Ceruloplasmin (CP) is a major multicopper-containing plasma protein that not only involved in iron metabolism through its ferroxidase activity but also functions as an antioxidant. However, physiological substrates for CP have been fully identified nor has the role of understood. The reaction nitric oxide (NO) with was investigated view nitrosothiol (RS-NO) formation. First, formation heavy metal- or CP-catalyzed RS-NO examined physiologically relevant concentrations NO and various thiol...
Objective Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and subtypes remains unclear. Here, we first performed GWAS clinically defined only. Methods A conducted with 945 patients 1213 controls Japanese male population, followed replication study 1048 1334 controls....
This report describes a potent and selective inhibitor of multidrug toxin extrusion (MATE) protein, pyrimethamine (PYR), examines its effect on the urinary biliary excretion typical Mate1 substrates in mice. In vitro inhibition studies demonstrated that PYR is mouse (m)Mate1 (<i>K</i><sub>i</sub> = 145 nM) among renal organic cation transporters mOctn1 mOctn2 > 30 μM), mOct1 3.6 mOct2 6.0 μM). inhibited uptake metformin by kidney brush-border membrane vesicles (BBMVs) 41 canalicular...
Citrate plays a pivotal role not only in the generation of metabolic energy but also synthesis fatty acids, isoprenoids, and cholesterol mammalian cells. Plasma levels citrate are highest (∼135 μm) among intermediates tricarboxylic acid cycle. Here we report on cloning functional characterization plasma membrane transporter (NaCT for Na+-coupled transporter) from rat brain that mediates uphill cellular uptake coupled to an electrochemical Na+ gradient. NaCT consists 572 amino acids exhibits...
The aim of this study was to examine the mechanism underlying elevation in serum creatinine levels caused by a novel des-fluoro(6)-quinolone antibacterial agent, DX-619, healthy subjects. hOCT2 showed prominent uptake (Km = 56.4 mmol/l) among renal organic ion transporters. DX-619 is potent inhibitor (Ki 0.94 µmol/l), hMATE1 (0.82 and hMATE2-K (0.10 µmol/l). pharmacokinetic model involving inhibition (model 1), hOCT2, MATE1 or MATE2-K 2) could predict individual subjects receiving DX-619....
Cimetidine is known to cause drug-drug interactions (DDIs) with organic cations in the kidney, and a previous clinical study showed that coadministration of cimetidine or probenecid fexofenadine (FEX) decreased its renal clearance. FEX was taken up into human kidney by anion transporter (hOAT) 3 (<i>SLC22A8</i>), but mechanism luminal efflux has not been clarified. The present examined molecular these DDIs. Saturable uptake observed slices, <i>K</i><sub>m</sub> <i>V</i><sub>max</sub> values...
Multidrug and toxin extrusion 1 (MATE1) MATE2-K are H+/organic cation exchangers mediating the efflux of cationic drugs into urine. N-methylnicotinamide (NMN) was found to be an endogenous substrate MATE1 (Michaelis constant (Km) 301 ± 18 µmol/l) (Km 422 63 as well a basolateral influx transporter, organic transporter 2 318 29 µmol/l). A potent MATE inhibitor, pyrimethamine, competitively inhibited uptake by with inhibition (Ki) values 83 15 56 11 nmol/l, respectively. The NMN human kidney...
Nucleobases are important compounds that constitute nucleosides and nucleic acids. Although it has long been suggested specific transporters involved in their intestinal absorption uptake other tissues, none of molecular entities have identified mammals to date. Here we describe identification rat Slc23a4 as the first sodium-dependent nucleobase transporter (rSNBT1). The mRNA rSNBT1 was expressed highly only small intestine. When transiently HEK293 cells, could transport uracil most...
The functional characteristics of human proton coupled folate transporter (hPCFT)/heme carrier protein (HCP) 1 were investigated. hPCFT/HCP1 expressed transiently in embryonic kidney 293 cells mediated the transport at an acidic extracellular pH 5.5 a manner independent Na<sup>+</sup> and insensitive to membrane potential, but its activity was absent near-neutral pH. Folate by hPCFT/hHCP1 saturable with <i>K</i><sub>m</sub> 1.67 μM extensively inhibited reduced folates, such as folinate,...
Proton-coupled folate transporter/heme carrier protein 1 (PCFT/HCP1) has recently been identified as a transporter that mediates the translocation of folates across cellular membrane by proton-coupled mechanism and suggested to be possible molecular entity carrier-mediated intestinal transport system. To further clarify its role in transport, we examined functional characteristics rat PCFT/HCP1 (rPCFT/HCP1) expressed Xenopus laevis oocytes compared with those system small intestine evaluated...
Colonic microbiota synthesize a considerable amount of thiamine in the form pyrophosphate (TPP). Recent functional studies from our laboratory have shown existence specific, high-affinity, and regulated carrier-mediated uptake system for TPP human colonocytes. Nothing, however, is known about molecular identity this system. Here we report on identification colonic as product SLC44A4 gene. We cloned cDNA epithelial NCM460 cells, which, upon expression ARPE19 led to significant (p < 0.01,...
Gout is a common disease caused by hyperuricemia, which shows elevated serum uric acid (SUA) levels. From viewpoint of urate handling in humans, gout patients can be divided into those with renal overload (ROL) intestinal underexcretion, and underexcretion (RUE) gout. Recent genome-wide association studies (GWAS) revealed an between SUA variant human monocarboxylate transporter 9 (MCT9/SLC16A9) gene. Although the function MCT9 remains unclear, mostly excreted via intestine kidney where...
Monocarboxylate transporter 7 (MCT7) is an orphan expressed in the liver, brain, and several types of cancer cells. It has also been reported to be a survival factor melanoma breast cancers. However, this mechanism not yet fully understood due MCT7's unidentified substrate(s). Therefore, here we sought identify MCT7 substrate(s) characterize transport mechanisms by analyzing amino acid HEK293T cells polarized Caco-2 Analysis acids revealed significant rapid reduction taurine from transfected...
We have cloned and functionally characterized an Na+-coupled citrate transporter from Caenorhabditis elegans (ceNAC-2). This shows significant sequence homology to Drosophila Indy the mammalian NaCT (now known as NaC2). When heterologously expressed in a cell line or Xenopus oocytes, ceNAC-2 mediates transport of various intermediates citric acid cycle. However, it transports tricarboxylate more efficiently than dicarboxylates such succinate, feature different that ceNAC-1 (formerly ceNaDC1)...
In the present study, we report on molecular cloning and functional characterization of mouse NaCT (Na+-coupled citrate transporter), orthologue Drosophila Indy. Mouse consists 572 amino acids is highly similar to rat human NaCTs in primary sequence. The nact gene coding for transporter approx. 23 kb long 12 exons. When expressed mammalian cells, cloned mediates Na+-coupled transport succinate. Competition experiments reveal that also recognizes other tricarboxylic acid cycle intermediates...