JBC:尼古丁效果具有受体特异性

长期暴露在含有尼古丁的环境时，尼古丁受体的数量会有所增加，这是一种能导致烟瘾的上调机制。以前人们认为产生烟瘾的过程和尼古丁受体类型无关，但目前有研究者发现并非如此：吸烟者体内尼古丁水平的短期和长期变化分别对不同的特定受体亚型产生影响。

大脑中尼古丁受体最主要的亚型是a4b2，当血液中尼古丁水平逐渐升高时，这些受体也上调。一般情况下，暴露在含有尼古丁环境后2-3小时这些受体开始增加，大约20小时后达到峰值。

由于分布范围相对较少，任何一种次要尼古丁受体亚型上调都很困难，但是William Green及其同事们成功地开发出一种表达a6b2尼古丁受体的细胞。然后，他们用这种细胞证明，此亚型受体也能随尼古丁上调，而且速度更快，暴露于尼古丁环境后数分钟a6b2受体就开始增加并在2小时后达到峰值。

此外，刺激此类受体产生变化所需的尼古丁量大约为a4b2受体的10倍，只有在吸烟时才能短期突破原来水平达到这种尼古丁含量水平。这些结果让人们从新的角度认识了吸烟的不同阶段，它说明有不同的受体分别调节尼古丁的暂时和长期效果。

生物谷推荐原始出处：

（JBC），Vol. 283, Issue 10, 6022-6032，Heather Walsh，William N. Green

Up-regulation of Nicotinic Receptors by Nicotine Varies with Receptor Subtype

Heather Walsh, Anitha P. Govind, Ryan Mastro, J. C. Hoda, Daniel Bertrand, Yolanda Vallejo, and William N. Green

Recent evidence suggests that in addition to 4β2 and 3-containing nicotinic receptors, 6-containing receptors are present in midbrain dopaminergic neurons and involved in the nicotine reward pathway. Using heterologous expression, we found that 6β2, like 3β2 and 4β2 receptors, formed high affinity epibatidine binding complexes that are pentameric, trafficked to the cell surface, and produced acetylcholine-evoked currents. Chronic nicotine exposure up-regulated 6β2 receptors with differences in up-regulation time course and concentration dependence compared with 4β2 receptors, the predominant high affinity nicotine binding site in brain. The 6β2 receptor up-regulation required higher nicotine concentrations than for 4β2 but lower than for 3β2 receptors. The 6β2 up-regulation occurred 10-fold faster than for 4β2 and slightly faster than for 3β2. Our data suggest that nicotinic receptor up-regulation is subtype-specific such that 6-containing receptors up-regulate in response to transient, high nicotine exposures, whereas sustained, low nicotine exposures up-regulate 4β2 receptors.