JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Griffin, G.
Right arrow Articles by Abood, M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Griffin, G.
Right arrow Articles by Abood, M. E.

Vol. 285, Issue 2, 553-560, May 1998

Evaluation of Cannabinoid Receptor Agonists and Antagonists Using the Guanosine-5'-O-(3-[35S]thio)-triphosphate Binding Assay in Rat Cerebellar Membranes1

Graeme Griffin, Peter J. Atkinson, Vincent M. Showalter, Billy R. Martin and Mary E. Abood

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia

Cannabinoid receptors are members of the superfamily of G protein-coupled receptors. Their activation has previously been shown to stimulate guanosine 5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgamma S) binding in a range of brain regions using both membrane preparations and autoradiography. This study evaluates the activities of structurally diverse cannabinoid receptor ligands in the GTPgamma S binding assay, comparing the relationship between receptor binding and activation and also examining efficacy differences between compounds. Using rat cerebellar membrane preparations, the effects of GDP concentration on GTPgamma S binding and the activities of a range of cannabinoid receptor ligands, including the CB1 selective antagonist SR141716A, were investigated. GDP concentration was found to have differing effects on cannabinoid-stimulated [35S]GTPgamma S binding depending on the nature of the agonist used. The stimulation produced by high efficacy compounds, such as CP 55,940 and WIN 55212-2, was increased by raising the GDP concentration, but that of a low efficacy agonist, (-)-Delta -tetrahydrocannabinol, was decreased. Of the cannabinoid compounds tested, a wide range of potencies (EC50) and levels of maximal stimulation (Emax) were observed. These ranged from CP 55,244 (Emax of 165, 148-183%, and an EC50 of 0.47, 0.22-0.96, nM) through (-)-Delta -tetrahydrocannabinol, cannabinol and anandamide, which produced no concentration-dependent stimulation of [35S]GTPgamma S binding under the same conditions. SR141716A competitively antagonized all the agonists against which it was tested, providing equilibrium dissociation constants (Kd values) in the sub-nanomolar range (0.06-0.40 nM), implicating a CB1 receptor mediated response. These results provide a more detailed characterization of the cannabinoid-stimulated [35S]GTPgamma S binding assay than has previously been reported.

0022-3565/98/2852-0553$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
S. D. McAllister, D. P. Hurst, J. Barnett-Norris, D. Lynch, P. H. Reggio, and M. E. Abood
Structural Mimicry in Class A G Protein-coupled Receptor Rotamer Toggle Switches: THE IMPORTANCE OF THE F3.36(201)/W6.48(357) INTERACTION IN CANNABINOID CB1 RECEPTOR ACTIVATION
J. Biol. Chem., November 12, 2004; 279(46): 48024 - 48037.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
A. C. Howlett, F. Barth, T. I. Bonner, G. Cabral, P. Casellas, W. A. Devane, C. C. Felder, M. Herkenham, K. Mackie, B. R. Martin, et al.
International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors
Pharmacol. Rev., June 1, 2002; 54(2): 161 - 202.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
N. A. Darmani
The Potent Emetogenic Effects of the Endocannabinoid, 2-AG (2-Arachidonoylglycerol) Are Blocked by Delta 9-Tetrahydrocannabinol and Other Cannnabinoids
J. Pharmacol. Exp. Ther., January 1, 2002; 300(1): 34 - 42.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. S. Breivogel, G. Griffin, V. Di Marzo, and B. R. Martin
Evidence for a New G Protein-Coupled Cannabinoid Receptor in Mouse Brain
Mol. Pharmacol., July 1, 2001; 60(1): 155 - 163.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. Griffin, Q. Tao, and M. E. Abood
Cloning and Pharmacological Characterization of the Rat CB2 Cannabinoid Receptor
J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 886 - 894.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
M. Glass and J. K. Northup
Agonist Selective Regulation of G Proteins by Cannabinoid CB1 and CB2 Receptors
Mol. Pharmacol., December 1, 1999; 56(6): 1362 - 1369.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. D. McAllister, G. Griffin, L. S. Satin, and M. E. Abood
Cannabinoid Receptors Can Activate and Inhibit G Protein-Coupled Inwardly Rectifying Potassium Channels in a Xenopus Oocyte Expression System
J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 618 - 626.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1998 by the American Society for Pharmacology and Experimental Therapeutics.