Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • 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

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
Drug Metabolism & Disposition

Advanced Search

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

A Comparison of the Expression and Metabolizing Activities of Phase I and II Enzymes in Freshly Isolated Human Lung Parenchymal Cells and Cryopreserved Human Hepatocytes

G. I. Somers, N. Lindsay, B. M. Lowdon, A. E. Jones, C. Freathy, S. Ho, A. J. M. Woodrooffe, M. K. Bayliss and G. R. Manchee
Drug Metabolism and Disposition October 2007, 35 (10) 1797-1805; DOI: https://doi.org/10.1124/dmd.107.015966
G. I. Somers
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
N. Lindsay
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B. M. Lowdon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. E. Jones
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Freathy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Ho
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. J. M. Woodrooffe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. K. Bayliss
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G. R. Manchee
  • 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
Loading

Abstract

The pulmonary and hepatic expression and catalytic activities of phase I and II drug-metabolizing enzymes were compared using human lung and liver tissue, and lung parenchymal cells (LPCs) and cryopreserved hepatocytes. Cytochrome P450 gene expression was generally lower in lung than in liver and CYP3A4 expression in lung was negligible. Esterase gene expression was similar in lung and liver. Expression of all sulfotransferase isoforms in lung was similar to or higher than that in liver. Lung tissue expressed low levels of UGT. However, the expression of UGT2A1 in lung was higher than that in liver. There was a range of catalytic activities in LPCs, including cytochrome P450, esterase, and sulfation pathways. Phase I activities were generally less than 10% of those determined in hepatocytes. Rates of ester hydrolysis and sulfation in LPCs were similar to those in hepatocytes. When measurable, glucuronidation in LPCs was present at very low levels, reflecting the gene expression data. The metabolism of salbutamol, formoterol, and budesonide was also investigated. Production of salbutamol-4-O-sulfate and budesonide oleate was observed in LPCs from at least two of three donor preparations studied. Formoterol sulfate and low levels of formoterol glucuronide were detected in one of three donors. In general, drug-metabolizing capability of LPCs is low compared with liver, although some evidence for substantial sulfation and deesterification capacity was observed. Therefore, these data support the use of this cell-based system for the investigation of key routes of xenobiotic metabolism in human lung parenchyma.

Footnotes

  • doi:10.1124/dmd.107.015966.

  • ABBREVIATIONS: SULT, sulfotransferase; BDP, beclomethasone dipropionate; BMP, beclomethasone monopropionate; P450, cytochrome P450; LPC, lung parenchymal cell; 7-EC, 7-ethoxycoumarin; EPHX, epoxide hydrolase; ER, ethoxyresorufin; 7-HC, 7-hydroxycoumarin; LC-MS/MS, liquid chromatography-tandem mass spectrometry; 4-MU, 4-methylumbelliferone; PCR, polymerase chain reaction; SRM, selected reaction monitoring; UGT, uridine glucuronosyltransferase.

    • Received March 26, 2007.
    • Accepted July 9, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

Log in using your username and password

Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 35 (10)
Drug Metabolism and Disposition
Vol. 35, Issue 10
1 Oct 2007
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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.
A Comparison of the Expression and Metabolizing Activities of Phase I and II Enzymes in Freshly Isolated Human Lung Parenchymal Cells and Cryopreserved Human Hepatocytes
(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.
Citation Tools
Research ArticleArticle

A Comparison of the Expression and Metabolizing Activities of Phase I and II Enzymes in Freshly Isolated Human Lung Parenchymal Cells and Cryopreserved Human Hepatocytes

G. I. Somers, N. Lindsay, B. M. Lowdon, A. E. Jones, C. Freathy, S. Ho, A. J. M. Woodrooffe, M. K. Bayliss and G. R. Manchee
Drug Metabolism and Disposition October 1, 2007, 35 (10) 1797-1805; DOI: https://doi.org/10.1124/dmd.107.015966

Citation Manager Formats

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

Share
Research ArticleArticle

A Comparison of the Expression and Metabolizing Activities of Phase I and II Enzymes in Freshly Isolated Human Lung Parenchymal Cells and Cryopreserved Human Hepatocytes

G. I. Somers, N. Lindsay, B. M. Lowdon, A. E. Jones, C. Freathy, S. Ho, A. J. M. Woodrooffe, M. K. Bayliss and G. R. Manchee
Drug Metabolism and Disposition October 1, 2007, 35 (10) 1797-1805; DOI: https://doi.org/10.1124/dmd.107.015966
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • The Time-course of Aldehyde Oxidase and the Reason Why it is Nonlinear
  • Apalutamide Absorption, Metabolism, and Excretion in Healthy Men, and Enzyme Reaction in Human Hepatocytes
  • A Novel Unified Approach to Predict Human Hepatic Clearance for Both Enzyme- and Transporter-Mediated Mechanisms Using Suspended Human Hepatocytes
Show more Articles

Similar Articles

  • 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 © 2019 by the American Society for Pharmacology and Experimental Therapeutics