Hina Takeuchi1, Masayoshi Suzuki1, Ryohei Goto2, Kenta Tezuka1, Holger Fuchs3, Naoki Ishiguro4, Tetsuya Terasaki1,2, Clemens Braun5, Yasuo Uchida6,7. 1. Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan. 2. Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. 3. Boehringer Ingelheim Pharma GmbH & Co. KG, Cardio-Metabolic Diseases, Biberach, Germany. 4. Nippon Boehringer Ingelheim. Co. Ltd, Kobe, Japan. 5. Boehringer Ingelheim Pharma GmbH & Co. KG, Drug Discovery Sciences, Biberach, Germany. clemens.braun@boehringer-ingelheim.com. 6. Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan. yasuo.uchida.c8@tohoku.ac.jp. 7. Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. yasuo.uchida.c8@tohoku.ac.jp.
Abstract
PURPOSE: The purpose of the present study was to quantitatively determine the expression of transporters, receptors and tight junction molecules at the blood-arachnoid barrier (BAB) and blood-spinal cord barrier (BSCB) in cervical, thoracic and lumbar spines from dogs. METHODS: The expression levels of 31 transporters, 3 receptors, 1 tight junction protein, and 3 marker proteins in leptomeninges and capillaries isolated from spines (3 male and 2 female dogs) were determined by quantitative Targeted Absolute Proteomics (qTAP). The units were converted from fmol/μg protein to pmol/cm (absolute abundance at the BAB and the BSCB in a 1 cm section of spine). RESULTS: The expression of MDR1 and BCRP were greater at the BSCB compared to the BAB (especially in the cervical cord), and the expressions at the lumbar BSCB were lower than that for the cervical BSCB. Among the organic anionic and cationic drug transporters, OAT1, OAT3, MRP1, OCT2 and MATE1/2 were detected only in the BAB, and not at the BSCB). The expression of these transporters was higher in the order: lumbar > thoracic > cervical BAB. The expressions of GLUT1, 4F2hc, EAAT1, 2, PEPT2, CTL1, and MCT1 at the BSCB of the cervical cord were higher than the corresponding values for the cervical BAB, and these values decreased in going down the spinal cord. CONCLUSION: These results provide a better understanding of the molecular mechanisms underlying the concentration gradients of drugs and endogenous substances in the cerebrospinal fluid and parenchyma of the spinal cord.
PURPOSE: The purpose of the present study was to quantitatively determine the expression of transporters, receptors and tight junction molecules at the blood-arachnoid barrier (BAB) and blood-spinal cord barrier (BSCB) in cervical, thoracic and lumbar spines from dogs. METHODS: The expression levels of 31 transporters, 3 receptors, 1 tight junction protein, and 3 marker proteins in leptomeninges and capillaries isolated from spines (3 male and 2 female dogs) were determined by quantitative Targeted Absolute Proteomics (qTAP). The units were converted from fmol/μg protein to pmol/cm (absolute abundance at the BAB and the BSCB in a 1 cm section of spine). RESULTS: The expression of MDR1 and BCRP were greater at the BSCB compared to the BAB (especially in the cervical cord), and the expressions at the lumbar BSCB were lower than that for the cervical BSCB. Among the organic anionic and cationic drug transporters, OAT1, OAT3, MRP1, OCT2 and MATE1/2 were detected only in the BAB, and not at the BSCB). The expression of these transporters was higher in the order: lumbar > thoracic > cervical BAB. The expressions of GLUT1, 4F2hc, EAAT1, 2, PEPT2, CTL1, and MCT1 at the BSCB of the cervical cord were higher than the corresponding values for the cervical BAB, and these values decreased in going down the spinal cord. CONCLUSION: These results provide a better understanding of the molecular mechanisms underlying the concentration gradients of drugs and endogenous substances in the cerebrospinal fluid and parenchyma of the spinal cord.
Authors: Xingrong Liu; Kristine Van Natta; Helen Yeo; Olga Vilenski; Paul E Weller; Philip D Worboys; Mario Monshouwer Journal: Drug Metab Dispos Date: 2008-12-30 Impact factor: 3.922
Authors: Xingrong Liu; Bill J Smith; Cuiping Chen; Ernesto Callegari; Stacey L Becker; Xi Chen; Julie Cianfrogna; Angela C Doran; Shawn D Doran; John P Gibbs; Natilie Hosea; Jianhua Liu; Frederick R Nelson; Mark A Szewc; Jeffrey Van Deusen Journal: Drug Metab Dispos Date: 2006-06-07 Impact factor: 3.922