Cote T E, Frey E A, Sekura R D
J Biol Chem. 1984 Jul 25;259(14):8693-8.
The D-2 dopamine receptor mediates inhibition of adenylate cyclase in rat intermediate lobe; this receptor is linked to cyclase by the inhibitory guanyl nucleotide-binding protein (Ni). The functioning of components in the inhibitory system was compared in control and pertussis toxin-treated tissues. (-)-N-n-Propylnorapomorphine ((-)-NPA), a dopamine agonist, and 5'-guanylyl imidodiphosphate (Gpp(NH)p), a nonhydrolyzable GTP analog, caused a dose-dependent inhibition of adenylate cyclase in control tissue. Pertussis toxin abolished dopamine receptor-mediated inhibition of adenylate cyclase but did not alter Gpp(NH)p-induced inhibition of cyclase. In control tissue, GTP blocked Gpp(NH)p inhibition of cyclase in the absence, but not in the presence of (-)-NPA. Following pertussis toxin treatment, GTP blocked the inhibitory effect of Gpp(NH)p either in the absence or in the presence of (-)-NPA. Pertussis toxin did not alter the number of dopamine receptors or the affinity of the receptor for [3H]spiroperidol, a dopamine antagonist. However, pertussis toxin decreased the potency of (-)-NPA in the binding assay and abolished the ability of GTP to affect agonist binding. Furthermore, pertussis toxin abolished the dopamine receptor-mediated inhibition of immunoreactive alpha-melanocyte-stimulating hormone release, and induced the ADP-ribosylation of the Mr = 41,000 subunit of Ni.
D-2多巴胺受体介导大鼠中间叶腺苷酸环化酶的抑制作用；该受体通过抑制性鸟苷酸结合蛋白（Ni）与环化酶相连。在对照组织和百日咳毒素处理的组织中比较了抑制系统中各成分的功能。多巴胺激动剂（-）-N-正丙基去甲阿朴吗啡（（-）-NPA）和不可水解的GTP类似物5'-鸟苷酰亚胺二磷酸（Gpp（NH）p）在对照组织中引起了腺苷酸环化酶的剂量依赖性抑制。百日咳毒素消除了多巴胺受体介导的腺苷酸环化酶抑制作用，但未改变Gpp（NH）p诱导的环化酶抑制作用。在对照组织中，GTP在不存在（-）-NPA时可阻断Gpp（NH）p对环化酶的抑制作用，但在存在（-）-NPA时则不能。百日咳毒素处理后，无论是否存在（-）-NPA，GTP均可阻断Gpp（NH）p的抑制作用。百日咳毒素未改变多巴胺受体的数量或受体对多巴胺拮抗剂[3H]螺哌啶醇的亲和力。然而，百日咳毒素降低了（-）-NPA在结合试验中的效力，并消除了GTP影响激动剂结合的能力。此外，百日咳毒素消除了多巴胺受体介导的免疫反应性α-黑素细胞刺激素释放的抑制作用，并诱导了Ni的Mr = 41,000亚基的ADP-核糖基化。
