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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Rodent habenulo-interpeduncular pathway expresses a large variety of uncommon nAChR subtypes, but only the alpha3beta4* and alpha3beta3beta4* subtypes mediate acetylcholine release.
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Rodent habenulo-interpeduncular pathway expresses a large variety of uncommon nAChR subtypes, but only the alpha3beta4* and alpha3beta3beta4* subtypes mediate acetylcholine release.

机译：啮齿动物habenulo-interpeduncular通路表达多种不常见的nAChR亚型，但是只有alpha3beta4 *和alpha3beta3beta4 *亚型介导乙酰胆碱的释放。

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摘要

Recent studies suggest that the neuronal nicotinic receptors (nAChRs) present in the habenulo-interpeduncular (Hb-IPn) system can modulate the reinforcing effect of addictive drugs and the anxiolytic effect of nicotine. Hb and IPn neurons express mRNAs for most nAChR subunits, thus making it difficult to establish the subunit composition of functional receptors. We used immunoprecipitation and immunopurification studies performed in rat and wild-type (+/+) and beta2 knock-out (-/-) mice to establish that the Hb and IPn contain significant beta2* and beta4* populations of nAChR receptors (each of which is heterogeneous). The beta4* nAChR are more highly expressed in the IPn. We also identified novel native subtypes (alpha2beta2*, alpha4beta3beta2*, alpha3beta3beta4*, alpha6beta3beta4*). Our studies on IPn synaptosomes obtained from +/+ and alpha2, alpha4, alpha5, alpha6, alpha7, beta2, beta3, and beta4(-/-) mice show that only the alpha3beta4 and alpha3beta3beta4 subtypes facilitate acetylcholine (ACh) release. Ligand binding, immunoprecipitation, and Western blotting studies in beta3(-/-) mice showed that, in the IPn of these mice, there is a concomitant reduction of ACh release and alpha3beta4* receptors, whereas the receptor number remains the same in the Hb. We suggest that, in habenular cholinergic neurons, the beta3 subunit may be important for transporting the alpha3beta4* subtype from the medial habenula to the IPn. Overall, these studies highlight the presence of a wealth of uncommon nAChR subtypes in the Hb-IPn system and identify alpha3beta4 and alpha3beta3beta4, transported from the Hb and highly enriched in the IPn, as the subtypes modulating ACh release in the IPn.
机译：最近的研究表明，存在于汉本洛-小足间（Hb-IPn）系统中的神经元烟碱受体（nAChRs）可以调节成瘾药物的增强作用和尼古丁的抗焦虑作用。 Hb和IPn神经元表达大多数nAChR亚基的mRNA，因此难以建立功能受体的亚基组成。我们使用在大鼠和野生型（+ / +）和beta2敲除（-/-）小鼠中进行的免疫沉淀和免疫纯化研究来确定Hb和IPn包含大量的nAChR受体的beta2 *和beta4 *种群（每个这是异构的）。 beta4 * nAChR在IPn中表达更高。我们还确定了新颖的天然亚型（alpha2beta2 *，alpha4beta3beta2 *，alpha3beta3beta4 *，alpha6beta3beta4 *）。我们对从+ / +和alpha2，alpha4，alpha5，alpha6，alpha7，beta2，beta3和beta4（-/-）小鼠获得的IPn突触体的研究表明，只有alpha3beta4和alpha3beta3beta4亚型可促进乙酰胆碱（ACh）释放。在beta3（-/-）小鼠中的配体结合，免疫沉淀和Western印迹研究表明，在这些小鼠的IPn中，ACh释放和alpha3beta4 *受体同时减少，而Hb中的受体数目保持不变。我们建议，在habenular胆碱能神经元中，β3亚基对于将α3beta4*亚型从内侧ha管运输到IPn可能很重要。总体而言，这些研究强调了Hb-IPn系统中存在大量罕见的nAChR亚型，并确定了从Hb转运并高度富集于IPn中的alpha3beta4和alpha3beta3beta4，作为调节IPn中ACh释放的亚型。

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