Dopamine D₃R are widely expressed in basal ganglia where interact with D₁R. D₃R potentiate cAMP accumulation and GABA release stimulated by D₁R in striatonigral neurons through “atypical” signaling. During dopaminergic denervation, D₃R signaling changes to a “typical” in which antagonizes the effects of D₁R, the mechanisms of this switching are unknown. D₃nf splice variant regulates membrane anchorage and function of D₃R and decreases in denervation; thus, it is possible that D₃R signaling switching correlates with changes in D₃nf expression and increases of membranal D₃R that mask D₃R atypical effects. We performed experiments in unilaterally 6‐hydroxydopamine lesioned rats and found a decrease in mRNA and protein of D₃nf, but not of D₃R in the denervated striatum. Proximity ligation assay showed that D₃R‐D₃nf interaction decreased after denervation, whereas binding revealed an increased B _max in D₃R. The new D₃R antagonized cAMP accumulation and GABA release stimulated by D₁R; however, in the presence of N‐Ethylmaleimide (NEM), to block G_i protein signaling, activation of D₃R produced its atypical signaling stimulating D₁R effects. Finally, we investigated if the typical and atypical effects of D₃R modulating GABA release are capable of influencing motor behavior. Injections of D₃R agonist into denervated nigra decreased D₁R agonist‐induced turning behavior but potentiated it in the presence of NEM. Our data indicate the coexistence of D₃R typical and atypical signaling in striatonigral neurons during denervation that correlated with changes in the ratio of expression of D₃nf and D₃R isoforms. The coexistence of both atypical and typical signaling during denervation influences motor behavior.

中文翻译：

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多巴胺能去神经支配期间纹状体黑质神经元中 D3 R 典型和非典型信号的共存。与 D3 nf 表达变化的相关性。

多巴胺 D ₃ R 在与 D ₁ R相互作用的基底神经节中广泛表达。D ₃ R通过“非典型”信号传导增强纹状体黑质神经元中D ₁ R刺激的 cAMP 积累和 GABA 释放。在多巴胺能去神经支配过程中，D ₃ R 信号转变成一种“典型”信号，其中拮抗 D ₁ R 的作用，这种转换的机制尚不清楚。D ₃ nf 剪接变体调节 D ₃ R 的膜锚定和功能并减少去神经支配；因此，D ₃ R 信号转换可能与 D ₃ nf 表达的变化和膜 D 的增加相关₃ R 掩盖了 D ₃ R 非典型效应。我们在单侧 6-羟基多巴胺损伤的大鼠中进行了实验，发现去神经支配的纹状体中 D ₃ nf 的mRNA 和蛋白质减少，但 D ₃ R没有减少。邻近连接试验表明，去神经支配后D ₃ R-D ₃ nf 相互作用降低，而结合显示D ₃ R 中的B _max增加。新的 D ₃ R 拮抗 D ₁ R刺激的 cAMP 积累和 GABA 释放；然而，在 N-乙基马来酰亚胺 (NEM) 的存在下，为了阻断 G _i蛋白信号，激活 D ₃R 产生其非典型信号刺激 D ₁ R 效应。最后，我们调查了 D ₃ R 调节 GABA 释放的典型和非典型效应是否能够影响运动行为。将 D ₃ R 激动剂注射到去神经支配的黑质中会降低 D ₁ R 激动剂诱导的转动行为，但在 NEM 存在下会增强它。我们的数据表明，在去神经支配期间，纹状体黑质神经元中D ₃ R 典型和非典型信号的共存与 D ₃ nf 和 D ₃ R 同种型表达比率的变化相关。去神经支配期间非典型和典型信号的共存会影响运动行为。