文摘
大麻素受体的决心和表征大脑报道。生物活性二环大麻素止痛的cp - 55940是出现高特定活动。约束条件建立了老鼠大脑P2膜和突触体。7和8之间的最佳pH值是,和特定的绑定可以通过加热膜消除60度。绑定P2膜的范围内是线性10到50毫克的蛋白质/毫升。特定的绑定(定义为总绑定1 microMδ9-tetrahydrocannabinol流离失所(δ9-THC)或100海里desacetyllevonantradol)是饱和的。Kd确定从133年Scatchard分析点,和大鼠皮质Bmax P2膜1.85 pmol /毫克的蛋白质。希尔系数[3 h] cp - 55940接近1,表明,试验条件下,单个类结合位点的确定,没有表现出协同。绑定是快速(今敏大约2.6 x 10 (4) pm1最低为1)和可逆(Koff大约0.016最低为1)和(Koff大于0.06最低为1)。动力学常数的两个Kd值估计大约55点到超过200点,分别。 The binding of the agonist ligand [3H]CP-55,940 was decreased by the nonhydrolyzable GTP analog guanylylimidodiphosphate. The guanine nucleotide induced a more rapid dissociation of the ligand from the binding site, consistent with an allosteric regulation of the putative receptor by a G protein. The binding was also sensitive to MgCl2 and CaCl2. Binding of [3H]CP-55,940 was displaced by cannabinoid drugs in the following order of potency: CP-55,940 greater than or equal to desacetyllevonantradol greater than 11-OH-delta 9-THC = delta 9-THC greater than cannabinol. Cannabidiol and cannabigerol displaced [3H]CP-55,940 by less than 50% at 1 microM concentrations. The (-)-isomer of CP-55,940 displaced with 50-fold greater potency than the (+)-isomer. This pharmacology is comparable to both the inhibition of adenylate cyclase in vitro and the analgetic activity of these compounds in vivo. The criteria for a high affinity, stereoselective, pharmacologically distinct cannabinoid receptor in brain tissue have been fulfilled.