Biochemical and pharmacological characterization of cannabinoid binding sites using [3H]SR141716A.
This study describes the binding characteristics of cannabinoid binding sites expressed in rat cerebellar membranes using the tritiated derivative of SR141716A, the newly described cannabinoid receptor antagonist. A single population of high-affinity binding sites (K(D) = 0.59 +/- 0.08 nM; Bmax = 3.86 +/- 0.42 pmol mg-1 of protein) was demonstrated. Kinetic, competition and saturation experiments give similar results in terms of SR141716A affinity. delta 9-tetrahydrocannabinol and the 11-hydroxy derivative competitively inhibited the specific binding of [3H]SR141716A (Ki = 47 +/- 9 and 32 +/- 4 nM, respectively). The cannabinoid agonist WIN55212-2 has a 25-fold lower affinity for [3H]SR141716A than for [3H]WIN55212-2, showing that the two ligands do not recognize the cannabinoid binding site in the same fashion.
Petitet
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F
Rhône-Poulenc Rorer, CRVA, Vitry sur Seine, France.
Marin
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L
Doble
A
A
D000700:Analgesics / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D048588:Benzoxazines; D001667:Binding, Competitive / Q000187:drug effects; D002186:Cannabinoids / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009025:Morpholines / Q000378:metabolism / Q000493:pharmacokinetics; D009281:Naphthalenes / Q000378:metabolism / Q000493:pharmacokinetics; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism*; D000077285:Rimonabant
D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; 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; D000077285:Rimonabant