NICOTINE MEDIATED SODIUM FLUX IN PRIMARY CULTURES
NICOTINE MEDIATED SODIUM FLUX IN PRIMARY CULTURES
批准号:
3424098
负责人:
Barbara J Morley
金额:
$7.16万
依托单位国家:
美国
项目类别:
财政年份:
1991
资助国家:
美国
项目状态:
已结题
起止时间:
1991-03-01 至 1993-10-31
关键词:
acetylcholine affinity chromatography brain cell brain mapping brain metabolism cholinergic receptors electrophysiology hippocampus in situ hybridization laboratory rat membrane transport proteins neurophysiology neurotransmitter receptor neurotrophic factors nicotine nicotinic receptors potassium channel sodium channel tissue /cell culture
中文摘要
80%的戒烟者在一年内复发。尽管在那里
卷烟中的有效成分--复吸有很多原因,
尼古丁具有成瘾物质的特性。的所有动作
尼古丁尚不为人所知,但已知尼古丁在体内充当受体部位。
神经组织。它在乙酰胆碱受体部位的作用可能与
其令人上瘾的特性。
哺乳动物大脑中的烟碱型乙酰胆碱受体尚未被
刻画得很好。尼古丁与AT具有高亲和力(Kd1-10 nM)结合
至少一组大脑尼古丁受体。高亲和力
与脑组织的结合是一个悖论。电生理学研究表明
微摩尔浓度的尼古丁是受体所必需的
激活。有人认为大脑的感受器是不敏感的。
在测定过程中(其中10-20 NM浓度的尼古丁
被使用),表明K-激活(K-
哺乳动物烟碱受体的ACT)和K-脱敏(K-DES)
大脑。
我们实验室以前的工作表明,PC12的K-ACT和K-DES
具有良好特征的神经元感受器的细胞是7.7倍
10(5)M和8.2×10(5)M。根据这些数据,我们
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。
在活体内。因此,我们建议在初级神经元中研究这个问题。
脑培养采用22Na+内流。
~(22)Na~+内流在初级神经元中尚未被证实
培养物来源于哺乳动物的大脑。因此,本研究的目的是
是证明尼古丁受体介导的~(22)Na“在哺乳动物中的内流
脑文化。用~(22)Na+内流和尼古丁、胱氨酸作为
将进行激动剂以确定K-ACT和K-DES
感受器。还将在尼古丁存在的情况下进行流入
对抗者。这些实验将作为未来投资的基础--
大脑烟碱受体的生理特性。
英文摘要
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.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
Solid-phase peptide synthesis and biological activity of bovine thymopoietin II (bTP-II).
牛胸腺生成素 II (bTP-II) 的固相肽合成和生物活性。
DOI:
10.1111/j.1399-3011.1994.tb00574.x
发表时间:
1994
期刊:
International journal of peptide and protein research
影响因子:
--
作者:
[Smith,DD, Conlon,JM, Petzel,J, Chen,L, Murphy,RF, Morley,BJ]
通讯作者:
Morley,BJ
TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN
-
批准号:7850360
-
项目类别:
-
资助金额:$19.76万
-
财政年份:2009
-
负责人:Barbara J Morley
-
依托单位:
TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN
-
批准号:7320265
-
项目类别:
-
资助金额:$26.39万
-
财政年份:2005
-
负责人:Barbara J Morley
-
依托单位:
TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN
-
批准号:7035598
-
项目类别:
-
资助金额:$27.54万
-
财政年份:2005
-
负责人:Barbara J Morley
-
依托单位:
TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN
-
批准号:7707952
-
项目类别:
-
资助金额:$26.13万
-
财政年份:2005
-
负责人:Barbara J Morley
-
依托单位:
TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN
-
批准号:7585844
-
项目类别:
-
资助金额:$13.23万
-
财政年份:2005
-
负责人:Barbara J Morley
-
依托单位:
TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN
-
批准号:7154105
-
项目类别:
-
资助金额:$26.74万
-
财政年份:2005
-
负责人:Barbara J Morley
-
依托单位:
TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN
-
批准号:7533480
-
项目类别:
-
资助金额:$39.62万
-
财政年份:2005
-
负责人:Barbara J Morley
-
依托单位:
海外基金