A5026770912- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Antibiotics Pharmacokinetics and Efficacy
- Pharmacogenetics and Drug Metabolism
- Gout, Hyperuricemia, Uric Acid
- Adenosine and Purinergic Signaling
- Inflammatory mediators and NSAID effects
- Ion Transport and Channel Regulation
- Drug Solubulity and Delivery Systems
- Cancer therapeutics and mechanisms
- Peroxisome Proliferator-Activated Receptors
- HIV/AIDS drug development and treatment
- Gastroesophageal reflux and treatments
- Mitochondrial Function and Pathology
- RNA Interference and Gene Delivery
- Pregnancy and Medication Impact
- Neonatal Health and Biochemistry
- Radiopharmaceutical Chemistry and Applications
- Calcium signaling and nucleotide metabolism
- Antibiotic Resistance in Bacteria
- Advanced Drug Delivery Systems
- Folate and B Vitamins Research
- Trace Elements in Health
Kanazawa University
2015-2024
Kanazawa University Hospital
2023
Life Science Institute
2021
China Pharmaceutical University
2021
Ono Pharmaceutical (Japan)
2013-2018
Boehringer Ingelheim (Japan)
2017
University Hospital of Zurich
2016
University of Zurich
2016
University of Amsterdam
2016
Academic Medical Center
2016
Primary carnitine deficiency, because of a defect the tissue plasma membrane transporters, causes critical symptoms. However, transporter has not been molecularly identified. In this study, we screened human kidney cDNA library and assembled cDNA-encoding OCTN2 as homologue organic cation OCTN1, then examined function transporter. OCTN2-cDNA encodes polypeptide 557 amino acids with 75.8% similarity to OCTN1. Northern blot analysis showed that is strongly expressed in kidney, skeletal muscle,...
cDNA for a novel proton/organic cation transporter, OCTN1, was cloned from human fetal liver and its transport activity investigated. OCTN1 encodes 551-amino acid protein with 11 transmembrane domains one nucleotide binding site motif. It is strongly expressed in kidney, trachea, bone marrow several cancer cell lines, but not adult liver. When HEK293 cells, exhibited saturable pH-dependent [3H]tetraethyl ammonium uptake higher at neutral alkaline pH than acidic pH. Furthermore, treatment...
Some organic anions are absorbed from the gastrointestinal tract through carrier-mediated transport mechanism(s), which may include proton-coupled transport, anion exchange and others. However, molecular identity of transporters localized at apical membrane human intestinal epithelial cells has not been clearly demonstrated. In present study, we focused on transporting polypeptide OATP-B examined its subcellular localization functionality in small intestine. Localization was determined by...
Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate mechanism responsible for this reduction, SUA and urinary excretion rate of (UE(UA)) were analysed after oral administration luseogliflozin, a SGLT2 inhibitor, healthy subjects. After dosing, decreased, negative correlation was observed between level UE(UA), suggesting that decreased as result increase in UE(UA). The UE(UA) correlated with an D-glucose excretion, but...
Abstract Oxaliplatin is important for the clinical treatment of colorectal cancer and other gastrointestinal malignancies, but tumour resistance limiting. Several oxaliplatin transporters were previously identified their relative contributions to determining responses cell sensitivity remains unclear. We studied associations between expression transporter candidate genes patient response oxaliplatin, then experimentally verified found with MRP2 in models human cancer. Among 18 genes, was...
Urinary excretion accounts for two-thirds of total elimination uric acid and the remainder is excreted in feces. However, mechanism extra-renal poorly understood. In present study, we aimed to clarify extent through liver intestine using oxonate-treated rats Caco-2 cells as a model human intestinal epithelium. rats, significant amounts externally administered endogenous were recovered lumen, while biliary was minimal. Accordingly, direct secretion thought be substantial contributor acid....
The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for current coronavirus disease (COVID-19) pandemic. 3CL protease (3CLpro) plays a pivotal role in processing of viral polyproteins. We report peptidomimetic compounds with unique benzothiazolyl ketone warhead group, which display potent activity against SARS-CoV-2 3CLpro. most inhibitor YH-53 can strongly block replication. X-ray structural analysis revealed that establishes multiple hydrogen bond interactions...
Abstract We pharmacokinetically examined the effect of γ-butyrobetaine, a precursor l-carnitine, on change fatty acid metabolism in juvenile visceral steatosis (JVS) mice, which have systemic l-carnitine deficiency due to lack transporter activity. The concentrations total free (FFA), palmitic and stearic liver JVS mice were significantly higher than those wild-type mice. After intravenous administration γ-butyrobetaine (50 mg kg−1), concentration plasma reached about twice that control...
The pH-sensitive activity of human organic anion transporting polypeptide OATP-B, which is expressed at the apical membrane small intestinal epithelial cells, was functionally characterized. When initial uptake estrone-3-sulfate, a typical substrate OATP, studied kinetically, we observed an increase in <i>V</i><sub>max</sub> with decrease pH from 7.4 to 5.0, whereas change <i>K</i><sub>m</sub> negligible. OATP-B-mediated estrone-3-sulfate independent sodium, chloride, bicarbonate, or...
Genetic polymorphisms of human organic anion transporting polypeptides OATP-C (SLC21A6) and OATP-B (SLC21A9) in the Japanese population were analyzed. The allele frequencies <i>OATP-C*1a</i>,<i>OATP-C*1b</i> (N130D), <i>OATP-C*1c</i> (R152K D241N), <i>OATP-C*5</i> (V174A) 35.2, 53.7, 0, 0.7%, respectively, 267 healthy subjects. In the<i>OATP-C</i> gene, we found a novel called<i>OATP-C*15</i> possessing two single nucleotide (SNPs), N130D V174A, simultaneously. frequency of<i>OATP-C*15</i>...
Irinotecan hydrochloride (CPT-11) is a potent anticancer drug that converted to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), and other metabolites in liver. The disposition gastrointestinal toxicity of irinotecan exhibit wide interpatient variability. Here, we examined the contribution an organic anion-transporting polypeptide, OATP1B1 (OATP-C), which transports variety drugs their from blood liver humans, hepatic irinotecan, SN-38, glucuronide conjugate (SN-38G) by using...
In the present study, functional characteristics of organic cation transporter (OCTN)1, which was cloned as pH-dependent tetraethylammonium (TEA) when expressed in mammalian human embryonic kidney (HEK)293 cells, were further investigated using Xenopus oocytes well HEK293 cells gene expression systems. When OCTN1-derived complementary RNA injected into oocytes, transport [14C]TEA observed same cells. contrast, a replacement sodium ions with potassium surrounding medium did not cause any...
Carnitine is essential for β-oxidation of fatty acids, and a defect cell membrane transport carnitine leads to fatal systemic deficiency. We have already shown that the organic cation/carnitine transporter OCTN2 primary cause In present study, we further isolated characterized new members OCTN family, OCTN1 -3, in mice. All three were expressed commonly kidney, -2 also various tissues, whereas OCTN3 was by predominant expression testis. When their cDNAs transfected into HEK293 cells, cells...
Carnitine deficiency, either primary or drug-induced, causes critical symptoms and is thought to involve alteration of active transport carnitine across the plasma membrane tissues as underlying mechanism. Recently, we showed that human organic cation transporter, hOCTN2, cloned a member transporter family, physiologically important Na(+)-dependent high-affinity in humans. In this study, further characterized functional properties hOCTN2 examined interaction between hOCTN2-mediated...
Abstract Because the significance of P-glycoprotein in in-vivo secretion β-blockers intestinal epithelial cells is unclear, secretory mechanism for and other drugs has been evaluated. Uptake acebutolol, celiprolol, nadolol timolol, antiarrhythmic agent, quinidine by multidrug-resistant leukaemic cell line variant K562/ADM was significantly lower than that drug-sensitive K562 cells, suggesting these are transported out cells. The reduced uptake acebutolol drug-resistant reversed treating with...
It is believed that P-glycoprotein (P-gp) an energy-dependent drug efflux pump responsible for decreased accumulation in multidrug resistant (MDR) cells. In this study, we investigated whether azidopine, a photoactive dihydropyridine calcium channel blocker, transported by P-gp MDR Chinese hamster lung cells, DC-3F/VCRd-5L, and its binding site(s) on are distinct from those of Vinca alkaloids cyclosporins. The azidopine cells was inhibited the cytotoxic agent vinblastine (VBL). Cyclosporin A...