McAllister G, Knowles M R, Ward-Booth S M, Sinclair H A, Patel S, Marwood R, Emms F, Patel S, Smith A, Seabrook G R
Neuroscience Research Centre, Merck, Sharp & Dohme Research Laboratories, Harlow, Essex, UK.
J Recept Signal Transduct Res. 1995 Jan-Mar;15(1-4):267-81. doi: 10.3109/10799899509045220.
The D2 dopamine receptor is known to be functionally coupled to the inhibition of adenylate cyclase when expressed in a number of mammalian cell lines. However, functional coupling of the recently discovered D3 and D4 dopamine receptor subtypes has been more difficult to demonstrate. In this study, human D2, D3 and D4 receptors were stably expressed separately in human embryonic kidney cells (HEK 293). In these cells, activation of D2, D3 or D4 receptors resulted in the inhibition of forskolin-stimulated adenylate cyclase activity in a dose responsive manner. This activation was prevented by pre-incubation of the cells expressing these receptors with the dopaminergic antagonist haloperidol. Radioligand binding studies using [3H]spiperone confirmed that the atypical neuroleptic clozapine has higher affinity for the human D4 receptor than the D3 or D4 receptors, although only 6-fold higher than the D2 receptor in this study. In addition, ribonuclease protection studies demonstrated the presence of D4 dopamine receptor mRNA in human brain regions.
已知D2多巴胺受体在多种哺乳动物细胞系中表达时，在功能上与腺苷酸环化酶的抑制作用相关联。然而，最近发现的D3和D4多巴胺受体亚型的功能偶联则更难证明。在本研究中，人D2、D3和D4受体分别在人胚肾细胞（HEK 293）中稳定表达。在这些细胞中，D2、D3或D4受体的激活导致福斯高林刺激的腺苷酸环化酶活性呈剂量依赖性抑制。用多巴胺能拮抗剂氟哌啶醇预孵育表达这些受体的细胞可阻止这种激活。使用[3H]螺哌隆的放射性配体结合研究证实，非典型抗精神病药物氯氮平对人D4受体的亲和力高于D3或D2受体，尽管在本研究中仅比D2受体高6倍。此外，核糖核酸酶保护研究证明人脑区域存在D4多巴胺受体mRNA。
