Nye J S, Seltzman H H, Pitt C G, Snyder S H
J Pharmacol Exp Ther. 1985 Sep;234(3):784-91.
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.
研究了[3H]-5'-三甲基铵δ8-四氢大麻酚（THC）[（3H）TMA]与大鼠神经元膜的结合。TMA是δ8THC在5'碳上修饰的带正电荷类似物，该分子部分对其精神活性不重要。未标记的TMA以与δ9THC相同的突触前方式抑制豚鼠回肠的场刺激收缩（IC50 = 1 microM）。[3H]TMA以高亲和力（KD = 89 nM）饱和且可逆地与脑膜结合，明显结合到一类位点（希尔系数，1.1）。最高的结合位点密度出现在脑中，但几个外周器官也显示出特异性结合。去污剂可溶解这些位点而不影响其药理特性。分子筛色谱显示[3H]TMA结合活性的双峰峰，表观分子量约为60,000道尔顿。δ9THC强烈（Ki = 27 nM）且立体选择性地竞争性抑制[3H]TMA结合。对于一些大麻素，行为和生理测试中的效力与其对[3H]TMA结合位点的亲和力平行。然而，几种非精神活性大麻素在结合位点具有活性。
