Cannabinoid agonists and antagonists discriminated by receptor binding in rat cerebellum.
1. The effect of allosteric regulators on the binding affinity of a number of cannabinoid receptor ligands of varying efficacy in the rat cerebellum was investigated. 2. Radioligand ([3H]-SR141716A) competition curves were constructed in the presence or absence of sodium ions, magnesium ions and guanine nucleotides. 3. It was found that the presence of these allosteric regulators did not affect the affinity of the two antagonists used but did cause a significant decrease in the affinity of full and partial agonists. 4. This reduction in affinity ranged from a 3.67 fold rightward shift of the displacement curve of a mixed agonist/antagonist (3-(6-cyano-2-hexynyl)-delta-8-tetrahydrocannabinol-O-823) to a 38 fold rightward shift for 3-(1, 1-dimethyl-6-dimethylcarboxamide)-delta-8-tetrahydrocannabinol (O-1125), a full agonist. 5. In summary, the results of this study suggest a simple method for the inference of functional data using the classical radioligand binding assay.
Griffin
G
G
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, VA 23298, USA. grgriffi@hsc.vcu.edu
Wray
E J
EJ
Martin
B R
BR
Abood
M E
ME
D000494:Allosteric Regulation; D000818:Animals; D048588:Benzoxazines; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000378:metabolism / Q000494:pharmacology; D009281:Naphthalenes / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077285:Rimonabant
D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C065365:CP 55244; D000077285:Rimonabant