High-affinity cannabinoid binding sites in brain membranes labeled with [3H]-5'-trimethylammonium delta 8-tetrahydrocannabinol.
J Pharmacol Exp Ther
; 234(3): 784-91, 1985 Sep.
Article
en En
| MEDLINE
| ID: mdl-2993595
ABSTRACT
The binding of [3H]-5'-trimethylammonium delta 8-tetrahydrocannabinol (THC) [( 3H]TMA) to rat neuronal membranes was studied. TMA is a positively charged analog of delta 8THC modified on the 5' carbon, a portion of the molecule not important for its psychoactivity. Unlabeled TMA inhibits field-stimulated contractions of the guinea-pig ileum (IC50 = 1 microM) in the same presynaptic manner as delta 9THC. [3H]TMA binds saturably and reversibly to brain membranes with high affinity (KD = 89 nM) to apparently one class of site (Hill coefficient, 1.1). Highest binding site density occurs in the brain, but several peripheral organs also display specific binding. Detergent solubilizes the sites without affecting their pharmacological properties. Molecular sieve chromatography reveals a bimodal peak of [3H]TMA binding activity of approximately 60,000 daltons apparent molecular weight. delta 9THC competitively inhibits [3H]TMA binding potently (Ki = 27 nM) and stereoselectively. For some cannabinoids potency in behavioral and physiological tests parallels their affinity for the [3H]TMA binding site. However, several nonpsychotropic cannabinoids are active at the binding site.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dronabinol
/
Encéfalo
Límite:
Animals
Idioma:
En
Revista:
J Pharmacol Exp Ther
Año:
1985
Tipo del documento:
Article