Ventura A L, Calvet G A
Department of Neurobiology, Universidade Federal Fluminense, Niteroi, Brazil.
Brain Res Dev Brain Res. 1992 Oct 23;69(2):199-205. doi: 10.1016/0165-3806(92)90160-x.
[3H]SCH 23390 bound with high affinity (Kd = 0.6 nM) and in a saturable manner (Bmax = 130 fmol/mg protein) to membrane preparations of the chick optic lobe. Pharmacological experiments, using several dopaminergic ligands, revealed that [3H]SCH 23390 bound stereospecifically to dopaminergic receptors of the D1 type in this tissue. Other experiments revealed that dopamine was able to induce cyclic AMP accumulation in the optic lobe (ED50 = 3 microM), an effect that was blocked by fluphenazine, a potent D1 antagonist (IC50 = 1.8 microM). The developmental profile of tissue dopamine-dependent cyclic AMP accumulation, however, was quite different from the differentiation pattern of [3H]SCH 23390 specific binding sites. While [3H]SCH 23390 binding sites increased 4-fold after the 12th embryonic day (E12), dopamine-dependent cyclic AMP accumulation was maximal in earlier stages, decreasing progressively after E10. In tissues from embryos at E16 or older, no difference was observed between basal and dopamine-stimulated levels of cyclic AMP. These data suggest that D1 receptors are coupled to adenylate cyclase in a limited period of the development of the optic lobe and that D1 receptors not coupled to the enzyme can be a common feature in the CNS.
[3H]SCH 23390以高亲和力(解离常数Kd = 0.6纳摩尔)且呈饱和状态(最大结合量Bmax = 130飞摩尔/毫克蛋白质)与鸡视叶的膜制剂结合。使用多种多巴胺能配体进行的药理学实验表明,[3H]SCH 23390在该组织中立体特异性地结合于D1型多巴胺能受体。其他实验表明,多巴胺能够诱导视叶中环磷酸腺苷(cAMP)的积累(半数有效浓度ED50 = 3微摩尔),这一效应可被强效D1拮抗剂氟奋乃静阻断(半数抑制浓度IC50 = 1.8微摩尔)。然而,组织中多巴胺依赖性cAMP积累的发育模式与[3H]SCH 23390特异性结合位点的分化模式有很大不同。虽然[3H]SCH 23390结合位点在胚胎第12天(E12)后增加了4倍,但多巴胺依赖性cAMP积累在早期阶段达到最大值,在E10后逐渐下降。在E16或更大胚胎的组织中,未观察到基础cAMP水平和多巴胺刺激后cAMP水平之间的差异。这些数据表明,D1受体在视叶发育的有限时期内与腺苷酸环化酶偶联,并且未与该酶偶联的D1受体可能是中枢神经系统中的一个常见特征。