Characterization and distribution of binding sites for [3H]-SR 141716A, a selective brain (CB1) cannabinoid receptor antagonist, in rodent brain
| Autor: | Francis Barth, Jean-Claude Breliere, Gérard Le Fur, Françoise Pialot, Murielle Rinaldi-Carmona, Christian Congy, Philippe Soubrie, Elsa Redon, Andre Bachy |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Cannabinoid receptor medicine.drug_class Receptors Drug Population Mice Inbred Strains Pharmacology In Vitro Techniques Tritium Binding Competitive Sensitivity and Specificity General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley chemistry.chemical_compound Mice Piperidines In vivo medicine Animals Tissue Distribution General Pharmacology Toxicology and Pharmaceutics Binding site Receptor education Receptors Cannabinoid education.field_of_study Binding Sites Membranes Chemistry Brain General Medicine Anandamide Receptor antagonist Molecular biology Rats Cannabinoid receptor antagonist Pyrazoles Rimonabant Synaptosomes |
| Zdroj: | Life sciences. 58(15) |
| ISSN: | 0024-3205 |
| Popis: | SR 141716A belongs to a new class of compounds (diarylpyrazole) that inhibits brain cannabinoid receptors (CB1) in vitro and in vivo. The present study showed that [3H]-SR 141716A binds with high affinity (Kd=0.61 +/- 0.06 nM) to a homogenous population of binding sites (Bmax=0.72 +/- 0.05 pmol/mg of protein) in rate whole brain (minus cerebellum) synaptosomes. This specific binding was displaced by known cannabinoid receptor ligands with the following rank order of potency SR 141716ACP 55,940WIN 55212-2 = delta9-THCanandamide. Apart from anandamide, all these compounds were found to interact competitively with the binding sites labeled by [3H]-SR 141716A. On the other hand, agents lacking affinity for cannabinoid receptors were unable to displace [3H]-SR 141716A from its binding sites (IC5010 microM). In addition, the binding of [3H]-SR 141716A was insensitive to guanyl nucleotides. Regional rat brain distribution of CB1 cannabinoid receptors detected by [3H]-SR 141716A saturation binding and autoradiographic studies, showed that this distribution was very similar to that found for [3H]-CP 55,940. In vivo, the [3H]-SR 141716A binding was displaced by SR 141716A with ED50 values of 0.39 +/- 0.07 and 1.43 +/- 0.29 mg/kg following intraperitoneal and oral administration, respectively. Finally, the [3H]-SR 141716A binding sites remained significantly occupied for at least 12 hr following oral administration of 3 mg/kg SR 141716A. Taken together, these results suggest that SR 141716A in its tritiated form is a useful research tool for labeling brain cannabinoid receptors (CB1) in vitro and in vivo. |
| Databáze: | OpenAIRE |
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