On the interaction of gallamine with muscarinic receptor subtypes.
On the interaction of gallamine with muscarinic receptor subtypes.
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关于没食子胺与毒蕈碱受体亚型的相互作用。
DOI：
10.1016/0014-2999(90)90292-e
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发表时间：
1990
影响因子：
5
通讯作者：
R. Whiting
中科院分区：
文献类型：
--
作者：
A. Michel;R. Delmendo;M. López;R. Whiting
通过放射性配基结合研究，研究了胆碱能受体亚型与胆碱能受体的相互作用。在用[~3H]N-甲基东莨菪胺([~3H]NMS)进行的竞争研究中，加拉胺对大鼠心脏和豚鼠子宫M2 M_2受体以及鸡心中存在的非典型M_2受体表现出高亲和力。加拉胺对大鼠腺和人1321N1星形细胞瘤细胞的M3受体以及NG108-15和PC12细胞的M4受体均显示低亲和力。该化合物对[~3H]哌仑西平标记的大鼠大脑皮层M1受体具有中等亲和力。在确定亲和力估计所需的低浓度时，加拉胺与M1和M2受体的相互作用似乎是竞争性的。因此，与降低放射配基解离动力学所需的浓度相比，加拉胺抑制[~3H]吡伦西平与M1受体的结合和[~3H]NMS与M2受体的结合，分别低263倍和23倍。此外，在抑制63%到71%的特定放射性配基结合的浓度下，加拉胺对观察到的放射性配基与M1或M2受体的结合率没有影响。在M3腺体受体上，产生结合抑制作用的加拉胺浓度与降低[~3H]NMS结合和解离速率的浓度之间几乎没有分离。因此，很难确定在竞争研究中看到的对M3受体结合的抑制是通过竞争机制还是变构机制产生的。尽管它可能具有M3受体的变构性质，但加拉胺可以用来检测几种组织中M受体亚型的异质性，因此是确定M受体亚型的有用工具。
The interaction of gallamine with muscarinic receptor subtypes was examined using radioligand binding studies. In competition studies using [3H]N-methylscopolamine ([3H]NMS), gallamine displayed high affinity for the rat cardiac and guinea-pig uterine M2muscarinic receptors and for the atypical muscarinic receptor present in chicken heart. Gallamine displayed low affinity for rat glandular and human 1321 N1 astrocytoma cell M3receptors and also for the M4receptors of NG108-15 and PC12 cells. The compound displayed intermediate affinity for M1receptors of rat cortex labeled using [3H]pirenzepine. The interaction of gallamine with the M1and M2receptors appeared to be competitive at the low concentrations required to determine affinity estimates. Thus, gallamine inhibited the binding of [3H]pirenzepine to M1receptors and [3H]NMS to M2receptors at concentrations that were 263- and 23-fold lower, respectively, than those required to decrease radioligand dissociation kinetics. Furthermore, gallamine, at a concentration that inhibited between 63 and 71% of specific radioligand binding, had no effect on the observed rate of association of the radioligand with either the M1or the M2receptor. At the M3glandular receptor, there was little separation between the concentrations of gallamine that produced inhibition of binding and those that decreased the association and dissociation rates of [3H]NMS. It is therefore difficult to determine if the inhibition of binding seen in competition studies on the M3receptor was produced through a competitive or an allosteric mechanism. Despite its possible allosteric properties at the M3receptor, gallamine can be used to detect heterogeneity of muscarinic receptor subtypes in several tissues and therefore represents a useful tool for defining muscarinic receptor subtypes.
配体选择对没食子胺与心脏毒蕈碱受体的表观结合特征的影响。
DOI：
--
发表时间：
1988
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Lee,NH;el-Fakahany,EE
通讯作者：
el-Fakahany,EE
没食子胺对毒蕈碱受体发挥双相变构作用。
影响因子：
3.6
作者：
Ellis,J;Seidenberg,M
通讯作者：
Seidenberg,M
经典毒蕈碱拮抗剂的四元形式区分毒蕈碱受体亚群：与没食子胺定义的亚群的相关性。
DOI：
10.1016/0006-291x(85)90319-5
发表时间：
1985
影响因子：
3.1
作者：
Ellis,J;Lenox,RH
通讯作者：
Lenox,RH