Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here for more information

Sign In to gain access to subscriptions and/or personal tools.
Journal of Biomolecular Screening
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (5)
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Nuttall, M. E.
Right arrow Articles by Mattern, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nuttall, M. E.
Right arrow Articles by Mattern, M. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Amphibian Melanophore Technology as a Functional Screen for Antagonists of G-Protein Coupled 7-Transmembrane Receptors

Mark E. Nuttall

Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

John C. Lee

Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

Paul R. Murdock

Gene Expression Sciences, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park (North), Harlow, Essex, United Kingdom

Alison M. Badger

Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

Fei-Lan Wang

Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

Jeffrey T. Laydon

Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

Glenn A. Hofmann

Department of Biomolecular Discovery, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

Gary R. Pettman

Microbial and Cell Culture Sciences, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park (North), Harlow, Essex, United Kingdom

Jonathan A. Lee

Department of Protein Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

Ashu Parihar

NPS Pharmaceuticals, Salt Lake City, UT

Bradford C. Van Wagenen

NPS Pharmaceuticals, Salt Lake City, UT

John Fox

NPS Pharmaceuticals, Salt Lake City, UT

Maxine Gowen

Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

Randall K. Johnson

Department of Oncology Research, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

Michael R. Mattern

Department of Oncology Research, SmithKline Beecham Pharmaceuticals, King of Prussia, PA

Xenopus laevis melanophores stably expressing 7-transmembrane G-protein-coupled receptors were established and evaluated, either as a primary screening utility for antagonists of the human calcium receptor, or as a screen to assign function to binding inhibitors of human cannabinoid receptors. Stably or transiently expressing melanophores responded selectively to respective effectors of the human calcium, cannabinoid, and neurokinin-1 receptors. Several selective cannabinoid receptor-binding inhibitors of known potency were characterized as agonists or antagonists of the human peripheral cannabinoid (CB2) receptor. The results were consistent with changes in cAMP content of hCB2-transfected human embryonic kidney (HEK) cells challenged with the same CB2-binding antagonists. A stable melanophore cell line expressing the human calcium receptor was used to screen a compound collection directly for functional antagonists, several of which were confirmed as antagonists in secondary screens by stimulating parathyroid hormone (PTH) secretion from bovine parathyroid cells. The percentage of hits in this cell-based screen was reasonably low (1.2%), indicating minimal interference due to toxic effects and validating melanophores as a primary screening modality. Also described is the development of a novel procedure for cryopreservation and reconstitution of cells retaining functional human receptors.

Journal of Biomolecular Screening, Vol. 4, No. 5, 269-277 (1999)
DOI: 10.1177/108705719900400508
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J Biomol ScreenHome page
K. Moore and S. Rees
Cell-Based Versus Isolated Target Screening: How Lucky Do You Feel?
J Biomol Screen, April 1, 2001; 6(2): 69 - 74.
[PDF]