Bockaert J, Tassin J P, Thierry A M, Glowinski J, Premont J
Brain Res. 1977 Feb 11;122(1):71-86. doi: 10.1016/0006-8993(77)90663-1.
Homogenates of frontal cerebral cortex of the rat were prepared from microdiscs punched out in areas rich in dopaminergic terminals. Under optimal assay conditions, dopamine (10-4 M) stimulated an adenylate cyclase present in these homogenates by 80-100%. This stimulation reached 200% when microdiscs were punched out from the medial part of the frontal cerebral cortex, adjacent to the forceps minor. Dopamine interacted with an homogeneous population of receptor sites which had an apparent affinity (KD) of 3.8 +/- 0.9 x 10-6 M (N = 4). The dopamine receptor was blocked by fluphenazine and phentolamine but had no affinity for pindolol, propranolol or L-isoproterenol. The affinities of several neuroleptics having different chemical structures were simultaneously determined on striatal and on frontal cerebral cortex dopamine sensitive adenylate cyclases. Fluphenazine was more potent in blocking the striatal than the frontal cerebral cortex dopaminergic receptors. In contrast, in all experiments, haloperidol had an higher affinity for the cerebral frontal cortex than for the striatal dopaminergic receptors. Thus, haloperidol was less effective than fluphenazine in blocking the striatal dopaminergic receptors, and equally potent than fluphenazine in inhibiting the frontal cerebral cortex dopamine sensitive adenylate cyclase. Chlorpromazine, thioridazine and clozapine had the same affinity for the two dopaminergic adenylate cyclase systems. L-isoproterenol interacted with an homogeneous population of beta-adrenergic receptor sites (KD = 3 +/- 2 X 10-7 M; N = 4) coupled with an adenylate cyclase distince from the dopamine sensitive adenylate cyclase. This beta-receptor had no affinity for dopamine or fluphenazine but was blocked by propranolol or pindolol. L-Norepinephrine was shown to stimulate both the dopamine (KD = 1.8 +/- 1 X 10-5 M; N = 4) and the beta-adrenergic (KD = 8 +/- 3 X 10-7 M; N = 4) sensitive adenylate cyclases. Thus, the L-norepinephrine effect was totally blocked in the combined presence of fluphenazine and pindolol.
大鼠额叶皮质匀浆取自富含多巴胺能终末的区域冲压出的微盘。在最佳测定条件下，多巴胺（10⁻⁴ M）可使这些匀浆中的腺苷酸环化酶活性提高80% - 100%。当从额叶皮质内侧靠近小钳的部位冲压出微盘时，这种刺激作用可达200%。多巴胺与一群同质的受体位点相互作用，其表观亲和力（KD）为3.8 ± 0.9×10⁻⁶ M（N = 4）。多巴胺受体被氟奋乃静和酚妥拉明阻断，但对吲哚洛尔、普萘洛尔或L - 异丙肾上腺素无亲和力。同时测定了几种化学结构不同的抗精神病药物对纹状体和额叶皮质多巴胺敏感腺苷酸环化酶的亲和力。氟奋乃静阻断纹状体多巴胺能受体的作用比阻断额叶皮质多巴胺能受体更强。相反，在所有实验中，氟哌啶醇对大脑额叶皮质多巴胺能受体的亲和力高于对纹状体多巴胺能受体的亲和力。因此，氟哌啶醇在阻断纹状体多巴胺能受体方面比氟奋乃静效果差，而在抑制额叶皮质多巴胺敏感腺苷酸环化酶方面与氟奋乃静效力相当。氯丙嗪、硫利达嗪和氯氮平对两种多巴胺能腺苷酸环化酶系统的亲和力相同。L - 异丙肾上腺素与一群同质的β - 肾上腺素能受体位点相互作用（KD = 3 ± 2×10⁻⁷ M；N = 4），该受体与一种不同于多巴胺敏感腺苷酸环化酶的腺苷酸环化酶偶联。这种β - 受体对多巴胺或氟奋乃静无亲和力，但被普萘洛尔或吲哚洛尔阻断。L - 去甲肾上腺素可刺激多巴胺敏感腺苷酸环化酶（KD = 1.8 ± 1×10⁻⁵ M；N = 4）和β - 肾上腺素能敏感腺苷酸环化酶（KD = 8 ± 3×10⁻⁷ M；N = 4）。因此，在氟奋乃静和吲哚洛尔同时存在的情况下，L - 去甲肾上腺素的作用完全被阻断。
