Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Interspecies Variability in Expression of Hepatobiliary Transporters across Human, Dog, Monkey, and Rat as Determined by Quantitative Proteomics

Li Wang, Bhagwat Prasad, Laurent Salphati, Xiaoyan Chu, Anshul Gupta, Cornelis E.C.A. Hop, Raymond Evers and Jashvant D. Unadkat
Drug Metabolism and Disposition March 2015, 43 (3) 367-374; DOI: https://doi.org/10.1124/dmd.114.061580
Li Wang
Department of Pharmaceutics, University of Washington, Seattle, Washington (L.W., B.P., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Drug Metabolism and Pharmacokinetics, Infection DMPK, AstraZeneca Pharmaceuticals LLP, Waltham, Massachusetts (A.G.); and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bhagwat Prasad
Department of Pharmaceutics, University of Washington, Seattle, Washington (L.W., B.P., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Drug Metabolism and Pharmacokinetics, Infection DMPK, AstraZeneca Pharmaceuticals LLP, Waltham, Massachusetts (A.G.); and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laurent Salphati
Department of Pharmaceutics, University of Washington, Seattle, Washington (L.W., B.P., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Drug Metabolism and Pharmacokinetics, Infection DMPK, AstraZeneca Pharmaceuticals LLP, Waltham, Massachusetts (A.G.); and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoyan Chu
Department of Pharmaceutics, University of Washington, Seattle, Washington (L.W., B.P., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Drug Metabolism and Pharmacokinetics, Infection DMPK, AstraZeneca Pharmaceuticals LLP, Waltham, Massachusetts (A.G.); and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anshul Gupta
Department of Pharmaceutics, University of Washington, Seattle, Washington (L.W., B.P., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Drug Metabolism and Pharmacokinetics, Infection DMPK, AstraZeneca Pharmaceuticals LLP, Waltham, Massachusetts (A.G.); and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cornelis E.C.A. Hop
Department of Pharmaceutics, University of Washington, Seattle, Washington (L.W., B.P., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Drug Metabolism and Pharmacokinetics, Infection DMPK, AstraZeneca Pharmaceuticals LLP, Waltham, Massachusetts (A.G.); and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raymond Evers
Department of Pharmaceutics, University of Washington, Seattle, Washington (L.W., B.P., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Drug Metabolism and Pharmacokinetics, Infection DMPK, AstraZeneca Pharmaceuticals LLP, Waltham, Massachusetts (A.G.); and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jashvant D. Unadkat
Department of Pharmaceutics, University of Washington, Seattle, Washington (L.W., B.P., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Drug Metabolism and Pharmacokinetics, Infection DMPK, AstraZeneca Pharmaceuticals LLP, Waltham, Massachusetts (A.G.); and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

We quantified, by liquid chromatography tandem mass spectrometry, transporter protein expression of BSEP, MATE1, MRP3, MRP4, NTCP, and OCT1 in our human liver bank (n = 55) and determined the relationship between protein expression and sex, age and genotype. These data complement our previous work in the same liver bank where we quantified the protein expression of OATPs, BCRP, MDR1, and MRP2. In addition, we quantified and compared the interspecies differences in expression of the hepatobiliary transporters, corresponding to the above human transporters, in liver tissue and hepatocytes of male beagle dogs, cynomolgus monkeys, Sprague-Dawley rats, and Wistar rats. In all the species, the sinusoidal OATPs/Oatps were the most abundant hepatic transporters. However, there were notable interspecies differences in the relative abundance of the remaining transporters. For example, the next most abundant transporter in humans and monkeys was OCT1/Oct1, whereas it was Mrp2 and Ntcp in dogs/Wistar rats and Sprague-Dawley rats, respectively. In contrast, the protein expression of the efflux transporters BCRP/Bcrp, MDR1/Mdr1, MRP3/Mrp3, MRP4/Mrp4, and MATE1/Mate1 was much lower across all the species. For most transporters, the expression in the liver tissues was comparable to that in the unplated cryopreserved hepatocytes. These data on human liver transporter protein expression complete the picture of the expression of major human hepatobiliary transporters important in drug disposition and toxicity. In addition, the data on expression of the corresponding hepatobiliary transporters in preclinical species will be helpful in interpreting and extrapolating pharmacokinetic, pharmacological, and toxicological results from preclinical studies to humans.

Footnotes

    • Received October 16, 2014.
    • Accepted December 22, 2014.
  • L.S., X.C., A.G., C.E.C.A.H., and R.E. contributed equally to the research.

  • This study was supported by the University of Washington Research Affiliate Program on Transporters (UWRAPT) sponsored by AstraZeneca, Genentech, and Merck & Co., Inc. (http://sop.washington.edu/uwrapt).

  • ↵dx.doi.org/10.1124/dmd.114.061580.

  • Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 43 (3)
Drug Metabolism and Disposition
Vol. 43, Issue 3
1 Mar 2015
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Interspecies Variability in Expression of Hepatobiliary Transporters across Human, Dog, Monkey, and Rat as Determined by Quantitative Proteomics
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Interspecies Variability in Hepatobiliary Transporters Expression

Li Wang, Bhagwat Prasad, Laurent Salphati, Xiaoyan Chu, Anshul Gupta, Cornelis E.C.A. Hop, Raymond Evers and Jashvant D. Unadkat
Drug Metabolism and Disposition March 1, 2015, 43 (3) 367-374; DOI: https://doi.org/10.1124/dmd.114.061580

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Interspecies Variability in Hepatobiliary Transporters Expression

Li Wang, Bhagwat Prasad, Laurent Salphati, Xiaoyan Chu, Anshul Gupta, Cornelis E.C.A. Hop, Raymond Evers and Jashvant D. Unadkat
Drug Metabolism and Disposition March 1, 2015, 43 (3) 367-374; DOI: https://doi.org/10.1124/dmd.114.061580
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • AKRs and GUSs in Testosterone Disposition
  • Olanzapine Glucuronidation in Humanized Mice
  • rs2242480 Regulates the Expression of CYP3A4 and CYP3A5
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics