Dopaminergic regulation of dopamine D3 and D3nf receptor mRNA expression.
Dopaminergic regulation of dopamine D3 and D3nf receptor mRNA expression.
复制标题
DOI：
10.1002/syn.20770
复制
发表时间：
2010-08
期刊：
影响因子：
2.3
通讯作者：
McNamara, Robert K.
中科院分区：
文献类型：
--
作者：
Richtand, Neil M.;Liu, Yanghong;Ahlbrand, Rebecca;Sullivan, Juliana R.;Newman, Amy Hauck;McNamara, Robert K.
关键词：
多巴胺D3受体在所有多巴胺受体中具有最高的多巴胺亲和力，并且因此可以调节由体积传递介导的多巴胺信号传导。D3受体亚型表达的变化可能会改变D3受体的功能，但鲜为人知的是，关于D3亚型表达的协调多巴胺能刺激的扰动。为了确定多巴胺受体刺激和阻断对D3受体选择性剪接的影响，我们测定了D3受体拮抗剂NGB 2904和间接多巴胺激动剂安非他明治疗后D3和D3 nf亚型mRNA的表达。酪氨酸羟化酶（TH）mRNA的表达，多巴胺合成的限速酶，也被确定。D3拮抗剂NGB 2904处理6 h后，腹侧纹状体、前额叶皮质和海马中D3/D3 nf mRNA表达比例增加，24 h后海马和黑质/腹侧被盖中D3/D3 nf mRNA表达比例持续升高。苯丙胺处理后24 h，前额叶皮质D3 mRNA和D3 nf mRNA表达分别下降65%和71%，但差异无统计学意义。TH mRNA的表达不受D3拮抗剂NGB 2904的影响，但在腹侧纹状体，海马和前额皮质苯丙胺升高。这些研究结果提供了证据，改变D3受体刺激的适应性反应，涉及D3受体选择性剪接的变化。此外，这些数据表明，多巴胺合成的D3自身受体调节不涉及TH mRNA表达的调节。最后，观察调节TH mRNA表达的多巴胺终末领域提供了实验支持的模型，在适应突触活动的mRNA表达的局部控制。
Dopamine D3 receptors have the highest dopamine affinity of all dopamine receptors, and may thereby regulate dopamine signaling mediated by volume transmission. Changes in D3 receptor isoform expression may alter D3 receptor function, however little is known regarding coordination of D3 isoform expression in response to perturbations in dopaminergic stimulation. In order to determine the effects of dopamine receptor stimulation and blockade on D3 receptor alternative splicing, we determined D3 and D3nf isoform mRNA expression following treatment with the D3 receptor antagonist NGB 2904, and the indirect dopamine agonist amphetamine. Expression of tyrosine hydroxylase (TH) mRNA, the rate-limiting enzyme in dopamine synthesis, was also determined. The D3/D3nf mRNA expression ratio was increased in ventral striatum, prefrontal cortex and hippocampus six hours following D3 antagonist NGB 2904 treatment, and remained persistently elevated at 24 hours in hippocampus and substantia nigra/ ventral tegmentum. D3 mRNA decreased 65% and D3nf mRNA expression decreased 71% in prefrontal cortex 24 hours following amphetamine treatment, however these changes did not reach statistical significance. TH mRNA expression was unaffected by D3 antagonist NGB 2904, but was elevated by amphetamine in ventral striatum, hippocampus and prefrontal cortex. These findings provide evidence for an adaptive response to altered D3 receptor stimulation involving changes in D3 receptor alternative splicing. Additionally, these data suggest D3 autoreceptor regulation of dopamine synthesis does not involve regulation of TH mRNA expression. Finally, the observation of regulated TH mRNA expression in dopamine terminal fields provides experimental support for the model of local control of mRNA expression in adaptation to synaptic activity.
登录
查看更多内容
影响因子：
3.4
作者：
Fedele, E;Fontana, G;Raiteri, M
通讯作者：
Raiteri, M
影响因子：
4.8
作者：
Nimchinsky, EA;Hof, PR;Schmauss, C
通讯作者：
Schmauss, C
影响因子：
3.6
作者：
Pritchard, Laurel M.;Newman, Amy Hauck;Richtand, Neil M.
通讯作者：
Richtand, Neil M.
影响因子：
3.8
作者：
Pritchard, Laurel M.;Logue, Aaron D.;Richtand, Neil M.
通讯作者：
Richtand, Neil M.
影响因子：
7.6
作者：
Richtand, NM;Welge, JA;Berger, SP
通讯作者：
Berger, SP