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NICOTINE MEDIATED SODIUM FLUX IN PRIMARY CULTURES

原代培养物中尼古丁介导的钠通量

基本信息

批准号：
3424098
负责人：
Barbara J Morley
金额：
$ 7.16万
依托单位：
FATHER FLANAGAN'S BOYS' HOME
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-03-01 至 1993-10-31
项目状态：
已结题

项目摘要

Eighty percent of smokers who quit relapse within a year. Although there are many reasons for relapse, the active ingredient in cigarettes, nicotine, has properties of an addictive substance. All of the actions of nicotine are not known, but nicotine is known to act as receptor sites in nervous tissues. Its action at acetylcholine receptor sites may be related to its addictive properties. The nicotinic acetylcholine receptors in mammalian brain have not been well-characterized. Nicotine binds with high affinity (Kd 1-10 nM) to at least one population of brain nicotinic receptors. The high-affinity binding to brain tissue is a paradox. Electrophysiological studies suggest that micromolar concentrations of nicotine are necessary for receptor activation. It has been suggested that the brain receptors are desensitized during the assay procedure (in which 10-20 nM concentrations of nicotine are used), indicating a 1000-fold difference between the K-activation (K- act) and K-desensitization (K-des) of nicotinic receptors in mammalian brain. Previous work in our laboratory indicates that the K-act and K-des of PC12 cells, which possess a well-characterized neuronal receptor, are 7.7 X 10(5) M and 8.2 X 10(5) M, respectively. On the basis of these data, we question whether the K-des and K-act in brain tissue would differ by 3 orders of magnitude. This question cannot be resolved using brain tissue in vivo. We therefore propose to study this question in primary neuronal brain cultures using 22Na+ influx. 22Na+ influx has not previously been demonstrated in primary neuronal cultures derived from mammalian brain. Therefore, the goal of this research is to demonstrate nicotinic receptor mediated 22Na" influx in mammalian brain culture. Experiments using 22Na+ influx and nicotine and cytisine as agonists will be performed to determine the K-act and K-des of the receptors. Influx will be also carried out in the presence of nicotinic antagonists. These experiments will serve as the basis for future inves- tigations of the physiological properties of brain nicotinic receptors.

百分之八十的戒烟者在一年内复吸。虽然有很多原因导致复吸，香烟中的活性成分，尼古丁具有成瘾物质的特性。所有的行动，尼古丁是未知的，但尼古丁是已知的作为受体网站，神经组织其在乙酰胆碱受体部位的作用可能与它的成瘾特性。哺乳动物脑中的烟碱乙酰胆碱受体尚未被发现。特征鲜明的尼古丁以高亲和力（Kd 1-10 nM）结合至至少有一个群体的大脑烟碱受体。高亲和力与脑组织结合是一个悖论电生理研究表明微摩尔浓度的尼古丁对受体是必需的， activation.有人认为大脑的感受器被脱敏了在测定过程中（其中10-20 nM浓度的尼古丁使用），表明K-活化（K-活化）之间的1000倍差异。 act）和K-脱敏（K-des）个脑袋本实验室的前期工作表明，PC_（12）的K_（act）和K_（des 细胞，其中具有良好的特征神经元受体，是7.7 X 10（5）M和8.2 × 10（5）M。根据这些数据，我们我怀疑脑组织中的K-des和K-act是否会相差3 数量级。这个问题不能用脑组织来解决 in vivo.因此，我们建议在初级神经元中研究这个问题。使用22 Na+流入的脑培养物。 22 Na+内流以前未在原代神经元中得到证实。来自哺乳动物脑的培养物。因此，本研究的目的证明哺乳动物中烟碱受体介导的22 Na-内流脑文化使用22 Na+内流和尼古丁和金雀花碱作为激动剂将被执行，以确定K-act和K-des的受体。还将在烟碱存在下进行流入，对手。这些实验将作为未来投资的基础。脑烟碱受体的生理特性的激动。