Sibley D R, Monsma F J, Shen Y
Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, Maryland 20892.
Int Rev Neurobiol. 1993;35:391-415. doi: 10.1016/s0074-7742(08)60573-5.
Table I summarizes the properties of all of the dopamine receptors that have been cloned to date. Thus far, five different genes encoding pharmacologically distinct receptors have been identified and isolated. Based on their structural, pharmacological, and functional similarities, two of these, D1A and D1B (or D1 and D5), comprise the D1 subfamily. D2, D3, and D4 receptors represent a D2 subfamily whose members are also structurally and pharmacologically similar. In fact, given these considerations, it has been suggested that the D2, D3, and D4 receptors be termed the D2A, D2B, and D2C receptors, respectively, in recognition of their D2-like properties. Given the unexpected heterogeneity of the dopaminergic receptor system, it is logical to ask if there are other dopamine receptor subtypes remaining be identified. This seems probable, as the characteristics of the cloned subtypes do not match all of the properties of some dopamine receptors which have been previously investigated. For instance, there is extensive evidence that "D1-like" dopamine receptors exist which are linked to the activation of phospholipase C, phosphatidylinositol turnover, and Ca2+ mobilization. Dopamine, as well as several "D1-selective" agonists, has been shown to stimulate phosphatidylinositol turnover in both brain slices and kidney membranes (Felder et al., 1989; Undie and Friedman, 1990; Vyas et al., 1992), and injection of striatal mRNA into Xenopus oocytes leads to dopamine-stimulated phosphatidylinositol turnover and Ca2+ mobilization (Mahan et al., 1990). These dopamine receptors might be analogous to the alpha 1-adrenergic receptors which stimulate phospholipase C activity and might define a third distinct subfamily of dopamine receptors. There is also evidence for additional members of the D2 subfamily of receptors. Using gene transfer methods, a receptor with D2-like pharmacology has been identified and expressed but not yet sequenced (Todd et al., 1989). Also, a D2-related receptor has been characterized in kidney inner medulla membranes (Huo et al., 1991). It thus appears that there may be more dopamine receptor subtypes yet to be discovered.
表I总结了迄今已克隆的所有多巴胺受体的特性。到目前为止，已经鉴定并分离出五个编码药理学上不同受体的不同基因。基于它们在结构、药理学和功能上的相似性，其中两个，D1A和D1B（或D1和D5），构成了D1亚家族。D2、D3和D4受体代表一个D2亚家族，其成员在结构和药理学上也相似。事实上，考虑到这些因素，有人建议将D2、D3和D4受体分别称为D2A、D2B和D2C受体，以认可它们类似D2的特性。鉴于多巴胺能受体系统出人意料的异质性，很自然会问是否还有其他多巴胺受体亚型有待鉴定。这似乎是可能的，因为已克隆亚型的特征并不与先前研究的某些多巴胺受体的所有特性相匹配。例如，有大量证据表明存在与磷脂酶C激活、磷脂酰肌醇周转和Ca2+动员相关的“D1样”多巴胺受体。多巴胺以及几种“D1选择性”激动剂已被证明能刺激脑切片和肾膜中的磷脂酰肌醇周转（费尔德等人，1989年；温迪和弗里德曼，1990年；维亚斯等人，1992年），并且将纹状体mRNA注射到非洲爪蟾卵母细胞中会导致多巴胺刺激的磷脂酰肌醇周转和Ca2+动员（马汉等人，1990年）。这些多巴胺受体可能类似于刺激磷脂酶C活性的α1 - 肾上腺素能受体，并且可能定义了多巴胺受体的第三个不同亚家族。也有证据表明D2受体亚家族还有其他成员。使用基因转移方法，已鉴定并表达了一种具有D2样药理学特性的受体，但尚未进行测序（托德等人，1989年）。此外，在肾内髓质膜中已对一种与D2相关的受体进行了表征（霍等人，1991年）。因此，似乎可能还有更多多巴胺受体亚型有待发现。
