Journal ArticleDOI
Quantitative expression of human drug transporter proteins in lung tissues: Analysis of regional, gender, and interindividual differences by liquid chromatography–tandem mass spectrometry
Atsushi Sakamoto,Atsushi Sakamoto,Takehisa Matsumaru,Norio Yamamura,Yasuo Uchida,Masanori Tachikawa,Sumio Ohtsuki,Tetsuya Terasaki +7 more
TLDR
The protein expression profiles of pulmonary drug transporters and regional, gender, and interindividual differences were clarified and suggest that administration by inhalation may be viable and OCTN1 may be the best target transporter protein for pulmonary disease drug design.About:
This article is published in Journal of Pharmaceutical Sciences.The article was published on 2013-09-01. It has received 78 citations till now. The article focuses on the topics: Transport protein & Abcg2.read more
Citations
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Journal ArticleDOI
Non-Animal Models of Epithelial Barriers (Skin, Intestine and Lung) in Research, Industrial Applications and Regulatory Toxicology
Sarah Gordon,Mardas Daneshian,Joke A. Bouwstra,Francesca Caloni,Samuel Constant,Donna E. Davies,Gudrun Dandekar,Carlos A. Guzmán,Eric Fabian,Eleonore Haltner,Thomas Hartung,Thomas Hartung,Nina Hasiwa,Patrick Hayden,Helena Kandarova,Sangeeta Khare,Harald F. Krug,Carsten Kneuer,Marcel Leist,Guoping Lian,Uwe Marx,Marco Metzger,Katharina Ott,Pilar Prieto,Michael S. Roberts,Erwin Ludo Roggen,Tewes Tralau,Claudia Catharina Maria Van Den Braak,Heike Walles,Claus-Michael Lehr +29 more
TL;DR: An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers and to discuss future directions for both the development of new models and the refinement of existing test methods.
Journal ArticleDOI
Nucleoside transporter proteins as biomarkers of drug responsiveness and drug targets.
TL;DR: A state-of-the-art overview of the clinical evidence generated so far supporting the concept that nucleoside and nucleobase proteins can indeed be biomarkers suitable for diagnosis and/or prognosis is provided.
Journal ArticleDOI
Drug Resistance Mechanisms in Non-Small Cell Lung Carcinoma.
TL;DR: Molecular mechanisms that are potential drivers of resistance in non-small cell lung carcinoma are examined, which include resistance to molecular targeted therapies as well as conventional chemotherapy through the activity of multidrug resistance proteins.
Journal ArticleDOI
Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury.
Kyunghee Yang,Cen Guo,Jeffrey L. Woodhead,Robert L. St. Claire,Paul B. Watkins,Paul B. Watkins,Scott Q. Siler,Brett A. Howell,Kim L. R. Brouwer +8 more
TL;DR: Applications of SCH in studying hepatobiliary drug disposition and bile acid-mediated DILI are discussed and an example is presented to show how data generated in the SCH model were used to establish a quantitative relationship between intracellular bile acids and cytotoxicity, and how this information was incorporated into a systems pharmacology model for DilI prediction.
Journal ArticleDOI
Non-neuronal cholinergic airway epithelium biology.
TL;DR: Acetylcholine, a major regulator of airway function, is not solely produced by neurons but also by a variety of non-neurons cells including various airway epithelial cells utilizing a molecular machinery of acetyl cholinergic synthesis and release that differs from that of neurons.
References
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Journal ArticleDOI
Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR
TL;DR: Development and application of REST is explained, the usefulness of relative expression in real-time PCR using REST is discussed and the mathematical model used is based on the PCR efficiencies and the mean crossing point deviation between the sample and control group.
Journal Article
Principles and methods for the morphometric study of the lung and other organs.
Journal ArticleDOI
Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors
Yasuo Uchida,Sumio Ohtsuki,Yuki Katsukura,Chiemi Ikeda,Takashi Suzuki,Junichi Kamiie,Tetsuya Terasaki +6 more
Abstract: We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in human brain microvessels, that is, the blood-brain barrier (BBB). Brain microvessels were isolated from brain cortexes of seven males (16-77 years old) and protein expression of 114 membrane proteins was determined by means of a liquid chromatography-tandem mass spectrometric quantification method using recently established in-silico peptide selection criteria. Among drug transporters, breast cancer resistance protein showed the most abundant protein expression (8.14 fmol/μg protein), and its expression level was 1.85-fold greater in humans than in mice. By contrast, the expression level of P-glycoprotein in humans (6.06 fmol/μg protein) was 2.33-fold smaller than that of mdr1a in mice. The organic anion transporters reported in rodent BBB, that is, multidrug resistance-associated protein, organic anion transporter and organic anion-transporting polypeptide family members, were under limit of quantification in humans, except multidrug resistance-associated protein 4 (0.195 fmol/μg protein). Among detected transporters and receptors for endogenous substances, the glucose transporter 1 level was similar to that of mouse, while the L-type amino acid transporter 1 level was fivefold smaller than that of mouse. These findings should be useful for understanding human BBB function and its differences from that in mouse.
Journal ArticleDOI
Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family.
Ikumi Tamai,Jun-ichi Nezu,Hiroshi Uchino,Yoshimichi Sai,Asuka Oku,Miyuki Shimane,Akira Tsuji +6 more
TL;DR: Three novel transporters structurally belonging to the organic anion transporting polypeptide (OATP) family in humans are identified and OATP-C proved to be identical with the recently reported LST1/OatP-2.
Journal ArticleDOI
Expression of Thirty-six Drug Transporter Genes in Human Intestine, Liver, Kidney, and Organotypic Cell Lines
Constanze Hilgendorf,Gustav Ahlin,Annick Seithel,Per Artursson,Anna-Lena Ungell,Johan Karlsson +5 more
TL;DR: The comparison of rat and human tissue will help to explain the observed species differences in in vivo models, increase understanding of the impact of active transport processes on pharmacokinetics and distribution, and improve the quality of predictions from animal studies to humans.
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Membrane transporters in drug development.
Kathleen M. Giacomini,Shiew-Mei Huang,Donald J. Tweedie,Leslie Z. Benet,Kim L. R. Brouwer,Xiaoyan Chu,Amber Dahlin,Raymond Evers,Volker Fischer,Kathleen M. Hillgren,Keith Hoffmaster,Toshihisa Ishikawa,Dietrich Keppler,Richard B. Kim,Caroline A. Lee,Mikko Niemi,Joseph W. Polli,Yuicchi Sugiyama,Peter W. Swaan,Joseph A. Ware,Stephen H. Wright,Sook Wah Yee,Maciej J. Zamek-Gliszczynski,Lei Zhang +23 more