Literature DB >> 32310660

Comparison of Absolute Protein Abundances of Transporters and Receptors among Blood-Brain Barriers at Different Cerebral Regions and the Blood-Spinal Cord Barrier in Humans and Rats.

Yasuo Uchida1, Yuta Yagi1, Masaki Takao2,3, Mitsutoshi Tano2, Mina Umetsu1, Satoshi Hirano1, Takuya Usui1, Masanori Tachikawa1, Tetsuya Terasaki1.   

Abstract

This work was designed to clarify the absolute abundances of transporters and receptors at different cerebral regions of the blood-brain barriers (BBB) and blood-spinal cord barrier (BSCB) in humans and rats, using physiologically relevant units (pmol/g tissue and fmol/cm2); 39 and 29 proteins including tight-junction proteins and markers were quantified in human and rat capillary samples, respectively. Protein expression levels of almost all proteins were identical within a 2-fold range between BBB and BSCB in rats, while many proteins showed >2-fold smaller expression levels in BSCB than BBB in humans. Protein expression levels of transporters and receptors in humans were remarkably smaller than those in rats in both BBB and BSCB in units of pmol/g tissue and fmol/cm2. Protein expression levels (fmol/cm2) of MDR1 and BCRP at the BBB in humans were 9.88-fold and 5.23-fold smaller than those in rats, respectively. GLUT1 expression (pmol/g tissue) at cortical BBB in a human was 2.49- and 3.76-fold greater than that at white matter BBB and BSCB, respectively. INSR and LRP1 proteins were detected at cortical BBB, but not at white matter BBB or BSCB in humans. These findings throw light on regional differences and species differences in pharmacokinetics and physiological functions in the central nervous system.

Entities:  

Keywords:  blood−brain barrier (BBB); blood−spinal cord barrier (BSCB); fmol/cm2; pmol/g tissue; species difference

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Year:  2020        PMID: 32310660     DOI: 10.1021/acs.molpharmaceut.0c00178

Source DB:  PubMed          Journal:  Mol Pharm        ISSN: 1543-8384            Impact factor:   4.939


  9 in total

1.  Regional Differences in the Absolute Abundance of Transporters, Receptors and Tight Junction Molecules at the Blood-Arachnoid Barrier and Blood-Spinal Cord Barrier among Cervical, Thoracic and Lumbar Spines in Dogs.

Authors:  Hina Takeuchi; Masayoshi Suzuki; Ryohei Goto; Kenta Tezuka; Holger Fuchs; Naoki Ishiguro; Tetsuya Terasaki; Clemens Braun; Yasuo Uchida
Journal:  Pharm Res       Date:  2022-04-29       Impact factor: 4.200

Review 2.  In Vitro to In Vivo Extrapolation Linked to Physiologically Based Pharmacokinetic Models for Assessing the Brain Drug Disposition.

Authors:  Yukiko Murata; Sibylle Neuhoff; Amin Rostami-Hodjegan; Hiroyuki Takita; Zubida M Al-Majdoub; Kayode Ogungbenro
Journal:  AAPS J       Date:  2022-01-13       Impact factor: 4.009

3.  Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood-brain barrier and neurovascular unit.

Authors:  Richard F Keep; Hazel C Jones; Lester R Drewes
Journal:  Fluids Barriers CNS       Date:  2021-05-21

Review 4.  Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery.

Authors:  Kristiina M Huttunen; Tetsuya Terasaki; Arto Urtti; Ahmed B Montaser; Yasuo Uchida
Journal:  Pharm Res       Date:  2022-03-07       Impact factor: 4.580

Review 5.  Addressing BBB Heterogeneity: A New Paradigm for Drug Delivery to Brain Tumors.

Authors:  Jessica I Griffith; Sneha Rathi; Wenqiu Zhang; Wenjuan Zhang; Lester R Drewes; Jann N Sarkaria; William F Elmquist
Journal:  Pharmaceutics       Date:  2020-12-11       Impact factor: 6.321

Review 6.  Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.

Authors:  Kelsy L Nilles; Erica I Williams; Robert D Betterton; Thomas P Davis; Patrick T Ronaldson
Journal:  Int J Mol Sci       Date:  2022-02-08       Impact factor: 5.923

Review 7.  Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs).

Authors:  Johanna Huttunen; Santosh Kumar Adla; Magdalena Markowicz-Piasecka; Kristiina M Huttunen
Journal:  Pharmaceutics       Date:  2022-06-10       Impact factor: 6.525

8.  Mathematical Models of Blood-Brain Barrier Transport of Monoclonal Antibodies Targeting the Transferrin Receptor and the Insulin Receptor.

Authors:  William M Pardridge; Tom Chou
Journal:  Pharmaceuticals (Basel)       Date:  2021-06-03

9.  An Atlas of the Quantitative Protein Expression of Anti-Epileptic-Drug Transporters, Metabolizing Enzymes and Tight Junctions at the Blood-Brain Barrier in Epileptic Patients.

Authors:  Risa Sato; Kotaro Ohmori; Mina Umetsu; Masaki Takao; Mitsutoshi Tano; Gerald Grant; Brenda Porter; Anthony Bet; Tetsuya Terasaki; Yasuo Uchida
Journal:  Pharmaceutics       Date:  2021-12-09       Impact factor: 6.321

  9 in total

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