Department of Pharmacology, College of Pharmacy, Chonnam National University, Gwang-Ju 61186, Republic of Korea.
Int J Mol Sci. 2023 Apr 4;24(7):6742. doi: 10.3390/ijms24076742.
Dopamine receptors are classified into five subtypes, with DR and DR playing a crucial role in regulating mood, motivation, reward, and movement. Whereas DR are distributed widely across the brain, including regions responsible for motor functions, DR are primarily found in specific areas related to cognitive and emotional functions, such as the nucleus accumbens, limbic system, and prefrontal cortex. Despite their high sequence homology and similar signaling pathways, DR and DR have distinct regulatory properties involving desensitization, endocytosis, posttranslational modification, and interactions with other cellular components. In vivo, DR is closely associated with behavioral sensitization, which leads to increased dopaminergic responses. Behavioral sensitization is believed to result from DR desensitization, which removes the inhibitory effect of DR on related behaviors. Whereas DR maintains continuous signal transduction through agonist-induced receptor phosphorylation, arrestin recruitment, and endocytosis, which recycle and resensitize desensitized receptors, DR rarely undergoes agonist-induced endocytosis and instead is desensitized after repeated agonist exposure. In addition, DR undergoes more extensive posttranslational modifications, such as glycosylation and palmitoylation, which are needed for its desensitization. Overall, a series of biochemical settings more closely related to DR could be linked to DR-mediated behavioral sensitization.
多巴胺受体分为五种亚型，DR 和 DR 在调节情绪、动机、奖励和运动方面起着至关重要的作用。而 DR 广泛分布于大脑中，包括负责运动功能的区域，DR 主要存在于与认知和情感功能相关的特定区域，如伏隔核、边缘系统和前额叶皮层。尽管 DR 和 DR 具有高度的序列同源性和相似的信号通路，但它们具有不同的调节特性，涉及脱敏、内吞作用、翻译后修饰和与其他细胞成分的相互作用。在体内，DR 与行为敏感化密切相关，后者导致多巴胺能反应增加。行为敏感化被认为是由于 DR 脱敏引起的，DR 脱敏消除了 DR 对相关行为的抑制作用。而 DR 通过激动剂诱导的受体磷酸化、 arrestin 募集和内吞作用来维持持续的信号转导，从而使脱敏的受体循环和重新敏感化，而 DR 很少发生激动剂诱导的内吞作用，而是在反复暴露于激动剂后脱敏。此外，DR 经历更广泛的翻译后修饰，如糖基化和棕榈酰化，这是其脱敏所必需的。总之，一系列与 DR 更密切相关的生化环境可能与 DR 介导的行为敏感化有关。
