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

Effect of Gestational Age on mRNA and Protein Expression of Polyspecific Organic Cation Transporters during Pregnancy

Nora Lee, Mary F. Hebert, Bhagwat Prasad, Thomas R. Easterling, Edward J. Kelly, Jashvant D. Unadkat and Joanne Wang
Drug Metabolism and Disposition December 2013, 41 (12) 2225-2232; DOI: https://doi.org/10.1124/dmd.113.054072
Nora Lee
Departments of Pharmaceutics (N.L., B.P., E.J.K., J.D.U., J.W.), Pharmacy (M.F.H., T.R.E.), and Obstetrics and Gynecology (M.F.H., T.R.E.), and the Obstetric-Fetal Pharmacology Research Unit (N.L., M.F.H., T.R.E., J.W.), University of Washington, Seattle, Washington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mary F. Hebert
Departments of Pharmaceutics (N.L., B.P., E.J.K., J.D.U., J.W.), Pharmacy (M.F.H., T.R.E.), and Obstetrics and Gynecology (M.F.H., T.R.E.), and the Obstetric-Fetal Pharmacology Research Unit (N.L., M.F.H., T.R.E., J.W.), University of Washington, Seattle, Washington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bhagwat Prasad
Departments of Pharmaceutics (N.L., B.P., E.J.K., J.D.U., J.W.), Pharmacy (M.F.H., T.R.E.), and Obstetrics and Gynecology (M.F.H., T.R.E.), and the Obstetric-Fetal Pharmacology Research Unit (N.L., M.F.H., T.R.E., J.W.), University of Washington, Seattle, Washington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas R. Easterling
Departments of Pharmaceutics (N.L., B.P., E.J.K., J.D.U., J.W.), Pharmacy (M.F.H., T.R.E.), and Obstetrics and Gynecology (M.F.H., T.R.E.), and the Obstetric-Fetal Pharmacology Research Unit (N.L., M.F.H., T.R.E., J.W.), University of Washington, Seattle, Washington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edward J. Kelly
Departments of Pharmaceutics (N.L., B.P., E.J.K., J.D.U., J.W.), Pharmacy (M.F.H., T.R.E.), and Obstetrics and Gynecology (M.F.H., T.R.E.), and the Obstetric-Fetal Pharmacology Research Unit (N.L., M.F.H., T.R.E., J.W.), University of Washington, Seattle, Washington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jashvant D. Unadkat
Departments of Pharmaceutics (N.L., B.P., E.J.K., J.D.U., J.W.), Pharmacy (M.F.H., T.R.E.), and Obstetrics and Gynecology (M.F.H., T.R.E.), and the Obstetric-Fetal Pharmacology Research Unit (N.L., M.F.H., T.R.E., J.W.), University of Washington, Seattle, Washington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joanne Wang
Departments of Pharmaceutics (N.L., B.P., E.J.K., J.D.U., J.W.), Pharmacy (M.F.H., T.R.E.), and Obstetrics and Gynecology (M.F.H., T.R.E.), and the Obstetric-Fetal Pharmacology Research Unit (N.L., M.F.H., T.R.E., J.W.), University of Washington, Seattle, Washington
  • 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

Polyspecific organic cation (OC) transporters play important roles in the disposition of clinically used drugs, including drugs used during pregnancy. Pregnancy is known to alter the expression of drug-metabolizing enzymes and transporters, but its specific effect on OC transporters has not been well defined. Using quantitative polymerase chain reaction and liquid chromatography coupled with tandem mass spectrometry targeted proteomics, we determined the effect of pregnancy and gestational age on mRNA and protein expression of major OC transporters in the kidney, liver, and placenta in mice with timed pregnancies. Human organic cation transporter 3 (hOCT3) expression was further investigated in human placentas from the first and second trimesters and at term. Our results showed that pregnancy had a marginal effect on renal mouse organic cation transporter 1/2 (mOct1/2) expression but significantly reduced mouse multidrug and toxin extrusion transporter 1 (mMate1) expression by 20%–40%. Hepatic expression of mOct1 and mMate1 was minimally affected by pregnancy. Human and mouse placentas predominantly expressed OCT3 with little expression of OCT1/2, MATE1/2, and plasma membrane monoamine transporter (PMAT). The hOCT3 protein in first and second trimester and term placentas was quantified to be 0.23 ± 0.033, 0.38 ± 0.072, and 0.36 ± 0.099 fmol/μg membrane protein, respectively. In contrast with the moderate increase in hOCT3 protein during human pregnancy, mOct3 expression in the mouse placenta was highly dependent on gestational age. Compared with gestational day (gd) 10, placental mOct3 mRNA increased by 37-fold and 46-fold at gd 15 and 19, leading to a 56-fold and 128-fold increase in mOct3 protein, respectively. Our study provides new insights into the effect of pregnancy on the expression of polyspecific OC transporters and supports an important role of OCT3 in OC transport at the placental barrier.

Footnotes

    • Received August 6, 2013.
    • Accepted October 7, 2013.
  • This project was supported by the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant U10 HD047892] and the National Institutes of Health National Institute of General Medical Sciences, Pharmacological Sciences Training Grant [Grant T32 GM07750]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or the National Institutes of Health.

  • dx.doi.org/10.1124/dmd.113.054072.

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

  • Copyright © 2013 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: 41 (12)
Drug Metabolism and Disposition
Vol. 41, Issue 12
1 Dec 2013
  • 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.
Effect of Gestational Age on mRNA and Protein Expression of Polyspecific Organic Cation Transporters during Pregnancy
(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

Organic Cation Transporter Expression during Pregnancy

Nora Lee, Mary F. Hebert, Bhagwat Prasad, Thomas R. Easterling, Edward J. Kelly, Jashvant D. Unadkat and Joanne Wang
Drug Metabolism and Disposition December 1, 2013, 41 (12) 2225-2232; DOI: https://doi.org/10.1124/dmd.113.054072

Citation Manager Formats

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

Share
Research ArticleArticle

Organic Cation Transporter Expression during Pregnancy

Nora Lee, Mary F. Hebert, Bhagwat Prasad, Thomas R. Easterling, Edward J. Kelly, Jashvant D. Unadkat and Joanne Wang
Drug Metabolism and Disposition December 1, 2013, 41 (12) 2225-2232; DOI: https://doi.org/10.1124/dmd.113.054072
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

  • Endogenous substrates of rat organic cation transporters
  • Catabolism and Metabolism of ABBV-011, a Calicheamicin ADC
  • Gadoxetate-enhanced MRI and FXR in benign tumours
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