Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

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 (22)
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Witte, D. G.
Right arrow Articles by Hancock, A. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Witte, D. G.
Right arrow Articles by Hancock, A. A.
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?

Use of a Fluorescent Imaging Plate Reader-Based Calcium Assay to Assess Pharmacological Differences between the Human and Rat Vanilloid Receptor

David G. Witte

Global Pharmaceutical Research and Development, Neuroscience Research, Abbott Laboratories, Abbott Park, IL.

Steven C. Cassar

Global Pharmaceutical Research and Development, Neuroscience Research, Abbott Laboratories, Abbott Park, IL.

Jeffrey N. Masters

Global Pharmaceutical Research and Development, Neuroscience Research, Abbott Laboratories, Abbott Park, IL.

Timothy Esbenshade

Global Pharmaceutical Research and Development, Neuroscience Research, Abbott Laboratories, Abbott Park, IL.

Arthur A. Hancock

Global Pharmaceutical Research and Development, Neuroscience Research, Abbott Laboratories, Abbott Park, IL.

The cloned vanilloid receptor 1 (VR1) is a ligand-gated calcium channel that is believed to be the capsaicin-activated vanilloid receptor found in native tissues, based on similarities regarding molecular mass, tissue distribution, and electrophysiological properties. Using a Fluorescent Imaging Plate Reader (FLIPR), along with Fluo-3 to signal intracellular calcium levels ([Ca++]i), rat VR1 (rVR1) and a human orthologue (hVR1) were pharmacologically characterized with various VR1 ligands. HEK-293 cells, stably expressing rVR1 or hVR1, exhibited dose-dependent increases in [Ca++]i when challenged with capsaicin (EC50s {cong} 10 nM). Responses to capsaicin were blocked by the VR1 antagonist capsazepine and were dependent on VR1 expression. Potencies for 10 structurally diverse VR1 agonists revealed rVR1 potencies highly correlated to that of hVR1 (R2 = 0.973). However, a subset of agonists (tinyatoxin, gingerol, and zingerone) was approximately 10-fold more potent for rVR1 compared to hVR1. Schild analysis for blockade of capsaicin-induced responses by capsazepine was consistent with competitive antagonism, whereas ruthenium red displayed noncompetitive antagonism. Compared to rVR1, hVR1 was more sensitive to blockade by both antagonists. For both rVR1 and hVR1, time-response waveforms elicited by resiniferatoxin increased more gradually compared to other agonists. Tinyatoxin also displayed slow responses with hVR1 but showed rapid responses with rVR1. Thus, FLIPR technology can be used to readily reveal differences between rVR1 and hVR1 pharmacology with respect to potencies, efficacies, and kinetics for several VR1 ligands.

Journal of Biomolecular Screening, Vol. 7, No. 5, 466-475 (2002)
DOI: 10.1177/108705702237679
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. Pharmacol. Exp. Ther.Home page
B. R. Bianchi, R. El Kouhen, T. R. Neelands, C.-H. Lee, A. Gomtsyan, S. N. Raja, S. N. Vaidyanathan, B. Surber, H. A. McDonald, C. S. Surowy, et al.
[3H]A-778317 [1-((R)-5-tert-Butyl-indan-1-yl)-3-isoquinolin-5-yl-urea]: a Novel, Stereoselective, High-Affinity Antagonist Is a Useful Radioligand for the Human Transient Receptor Potential Vanilloid-1 (TRPV1) Receptor
J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 285 - 293.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. Cui, P. Honore, C. Zhong, D. Gauvin, J. Mikusa, G. Hernandez, P. Chandran, A. Gomtsyan, B. Brown, E. K. Bayburt, et al.
TRPV1 Receptors in the CNS Play a Key Role in Broad-Spectrum Analgesia of TRPV1 Antagonists.
J. Neurosci., September 13, 2006; 26(37): 9385 - 9393.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. El Kouhen, C. S. Surowy, B. R. Bianchi, T. R. Neelands, H. A. McDonald, W. Niforatos, A. Gomtsyan, C.-H. Lee, P. Honore, J. P. Sullivan, et al.
A-425619 [1-Isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a Novel and Selective Transient Receptor Potential Type V1 Receptor Antagonist, Blocks Channel Activation by Vanilloids, Heat, and Acid
J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 400 - 409.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. Appendino, L. De Petrocellis, M. Trevisani, A. Minassi, N. Daddario, A. S. Moriello, D. Gazzieri, A. Ligresti, B. Campi, G. Fontana, et al.
Development of the First Ultra-Potent "Capsaicinoid" Agonist at Transient Receptor Potential Vanilloid Type 1 (TRPV1) Channels and Its Therapeutic Potential
J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 561 - 570.
[Abstract] [Full Text] [PDF]