Creese I, Sibley D R, Leff S, Hamblin M
Fed Proc. 1981 Feb;40(2):147-52.
Receptor binding studies with a variety of dopaminergic ligands have confirmed behavioral and biochemical findings that the central nervous system and peripheral nervous system contain several dopamine receptor subtypes. These subtypes can be discriminated on the basis of their agonist-antagonist pharmacological specificities, linkage to adenylate cyclase, cellular location, regulation by guanine neucleotides and ions, and involvement in several human diseases. Although questions remain unanswered, progress is rapidly being made in equating the subgroupings arrived at by these different experimental approaches. Dopamine receptors are regulated by a number of factors. Acutely, guanine nucleotides and some ions regulate agonist but not antagonist binding and are essential for receptor coupling with adenylate cyclase. Chronically, changes in the level of dopaminergic stimulation modulate the number of at least some receptor subtypes, resulting in "up or down regulation." An increase in receptor number appears central to the pathology of Parkinson's disease, tardive dyskinesia, and perhaps schizophrenia. Animal models indicate that it may be possible to exploit inherent capabilities for receptor modulation in clinical therapy. The therapeutic precedents set by the indentification of distinct subtypes of adrenoreceptors. histamine, and cholinergic receptors portends and exciting future for dopamine receptor research.
使用多种多巴胺能配体进行的受体结合研究证实了行为学和生物化学研究结果，即中枢神经系统和外周神经系统含有多种多巴胺受体亚型。这些亚型可根据其激动剂 - 拮抗剂药理学特异性、与腺苷酸环化酶的联系、细胞定位、鸟嘌呤核苷酸和离子的调节作用以及在多种人类疾病中的作用来区分。尽管问题仍未得到解答，但在使这些不同实验方法得出的亚组分类相互等同方面正在迅速取得进展。多巴胺受体受多种因素调节。急性情况下，鸟嘌呤核苷酸和一些离子调节激动剂而非拮抗剂的结合，并且对于受体与腺苷酸环化酶的偶联至关重要。长期来看，多巴胺能刺激水平的变化会调节至少一些受体亚型的数量，导致“上调或下调”。受体数量增加似乎是帕金森病、迟发性运动障碍以及可能的精神分裂症病理过程的核心。动物模型表明，在临床治疗中利用受体调节的内在能力或许是可行的。肾上腺素能受体、组胺受体和胆碱能受体不同亚型的鉴定所开创的治疗先例预示着多巴胺受体研究的美好未来。
