HUMAN BRAIN NICOTINIC RECEPTORS AND NICOTINE ADDICTION

描述（申请人的摘要）：这是一个竞争的重新提交 更新以继续研究烟碱乙酰胆碱受体（nAChR）基因 吸烟者和非吸烟者的人体组织中的家族。主要网站为 烟草使用中的生物作用被认为是烟碱乙酰胆碱 受体（nAChR）。已知该复杂基因家族的表达是 与吸烟有关。nAChR定位于大脑和 外围，它们可能具有不同的功能。在最后一次融资中 在此期间，有几个主要的调查结果。1)高亲和力烟碱受体 在吸烟者的大脑和外周血细胞中上调。受体 大脑中的数字与吸烟的数量直接相关 每日2)我们发现人类低亲和力α-7 nAChR基因 是部分复制的，并在人脑和人脑中表达为mRNA。 外周血细胞在持续更新以来获得的数据中， 提交，我们已经4）[原文如此]表征了烟碱受体亚单位mRNA 原代人淋巴细胞和多形核细胞（PMN）中的组成，5） 表明高亲和力（nM）尼古丁结合在 吸烟者以剂量依赖性方式，和6）证实了非常高的亲和力（VHA， pM）吸烟者血细胞中的尼古丁结合活性。对《圣经》的批评 修改后的提案反映了审查人员的意见。我们现建议：（1） 确定表达的人α-7烟碱受体基因的功能 重复（dup-alpha-7），2）检测区域表达和功能 人体组织中非常高亲和力的尼古丁结合活性，3） 确定mRNA对全长α-7基因的贡献， dup-α-7基因和亚单位在外周血细胞中表达， 发现与吸烟习惯有关。

DESCRIPTION (applicant's abstract): This is a resubmission of a competing renewal to continue study of the nicotinic acetylcholine receptor (nAChR) gene family in human tissues of smokers and non-smokers. The principal site for biological action in tobacco use is thought to be the nicotinic acetylcholine receptors (nAChR). Expression of this complex gene family is known to be related in humans by smoking. nAChR are localized in both brain and in the periphery where they may have different functions. During the last funding period there were several major findings. 1) High affinity nicotinic receptors are up-regulated in human brain and peripheral blood cells of smokers. Receptor numbers in brain are directly correlated with the number of cigarettes smoked per day. 2) We have discovered that the human low affinity alpha-7 nAChR gene is partially duplicated, and is expressed as mRNA in both human brain and in peripheral blood cells. In data obtained since the continuing renewal was submitted, we have 4) [sic] characterized the nicotinic receptor subunit mRNA composition in primary human lymphocytes and polymorphonuclear cells (PMN), 5) shown that high affinity (nM) nicotine binding is regulated in the PMN of smokers in a dose dependent manner, and 6) confirmed a very high affinity (VHA, pM) nicotine binding activity in blood cells of smokers. The critiques of the reviewers are reflected in the modified proposal. We now propose 1) To determine the function of the expressed human alpha-7 nicotinic receptor gene duplication (dup-alpha-7), 2) To examine the regional expression and function of the very high affinity nicotine binding activity in human tissues, 3) To determine the contribution of mRNA for the full-length alpha-7 gene, the dup-alpha-7 gene and subunits expressed in peripheral blood cells where the VHA binding is found, to the smoking habit.