Kapsimali M, Dumond H, Le Crom S, Coudouel S, Vincent J D, Vernier P
UPR 2197, Institut de Neurobiologie A. Fessard, CNRS, Gif-sur-Yvette.
J Soc Biol. 2000;194(2):87-93.
Dopamine is a widespread neurotransmitter which exerts numerous neuromodulatory actions in the vertebrate central nervous system. This pleiotropic activity relies on the organisation of dopamine-synthesizing neuronal pathways and on a multiplicity of specific membrane receptors. A comparative approach has been undertaken to gain clues on the genetic events which took place during evolution to devise the dopamine systems of modern vertebrates. The localisation and phenotype of dopamine-synthesizing neurones is determined by different gene networks in each of the dopaminergic nuclei. However, despite this amazing diversity, the overall organisation of the dopaminergic nuclei is strinkingly conserved in the main vertebrates groups. In sharp contrast, the number of dopamine receptors subtypes has been multiplied by two major steps of gene duplications during vertebrates evolution. The first one occurred in the lineage leading to agnathans, whereas the second was concomitant to the emergence of cartilaginous fish. Accordingly, three subtypes exist in D1 receptor class (D1A, D1B, D1C) in all the jawed vertebrates, with two exceptions: eutherian mammals where only two D1 subtypes are found (D1A, D1B) and archosaurs where a fourth subtype is present (D1D). Comparisons of the pharmacological and biochemical characteristics of the dopamine receptors in vertebrate groups revealed homologous features that define each of the receptor subtypes and that have been fixed after gene duplications. The comparison of the distribution of the D1 receptor transcripts in the brain of teleosts and mammals points to significant conserved or derived expression territories, revealing previously neglected aspects of dopamine physiology in vertebrates.
多巴胺是一种广泛存在的神经递质,在脊椎动物中枢神经系统中发挥着多种神经调节作用。这种多效性活动依赖于多巴胺合成神经元通路的组织以及多种特定的膜受体。为了探寻在进化过程中发生的遗传事件的线索,从而构建现代脊椎动物的多巴胺系统,我们采用了比较研究方法。多巴胺合成神经元的定位和表型由每个多巴胺能核中的不同基因网络决定。然而,尽管存在这种惊人的多样性,多巴胺能核的整体组织在主要脊椎动物类群中却惊人地保守。与之形成鲜明对比的是,在脊椎动物进化过程中,多巴胺受体亚型的数量通过两个主要的基因复制步骤得以增加。第一个步骤发生在通向无颌类的谱系中,而第二个步骤与软骨鱼类的出现同时发生。因此,在所有有颌脊椎动物中,D1受体类存在三种亚型(D1A、D1B、D1C),但有两个例外:真兽类哺乳动物中仅发现两种D1亚型(D1A、D1B),而在恐龙中存在第四种亚型(D1D)。对脊椎动物类群中多巴胺受体的药理和生化特性进行比较,揭示了定义每个受体亚型且在基因复制后固定下来的同源特征。对硬骨鱼和哺乳动物大脑中D1受体转录本分布的比较表明,存在显著保守或衍生的表达区域,揭示了脊椎动物多巴胺生理学中先前被忽视的方面。