The binding of [3H]5'-trimethylammonium Δ8-tetrahydrocannabinol (THC) ([3H]TMA) to rat neuronal membranes was studied. TMA is a positively charged analog of Δ8THC 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 μM) in the same presynaptic manner as Δ9THC. [3H]TMA binds saturably and reversibly to brain membranes with high affinity (K(D) = 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. Δ9THC competitively inhibits [3H]TMA binding potently (K(i) = 27 nM) and stereoselectively. For some cannabinoids potency in behavioral and physiological tests parallels their affinity for the [3H]TMA binding sites. However, several nonpsychotropic cannabinoids are active at the binding site.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1985|
ASJC Scopus subject areas
- Molecular Medicine