Suppr超能文献

Epibatidine activates muscle acetylcholine receptors with unique site selectivity.

作者信息

Prince R J, Sine S M

机构信息

Receptor Biology Laboratory, Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905, USA.

出版信息

Biophys J. 1998 Oct;75(4):1817-27. doi: 10.1016/S0006-3495(98)77623-4.

Abstract

We recently showed that at desensitized muscle nicotinic receptors, epibatidine selects by 300-fold between the two agonist binding sites. To determine whether receptors in the resting, activatible state show similar site selectivity, we studied epibatidine-induced activation of mouse fetal and adult receptors expressed in 293 HEK cells. Kinetic analysis of single-channel currents reveals that (-)-epibatidine binds with 15-fold selectivity to sites of adult receptors and 75-fold selectivity to sites of fetal receptors. For each receptor subtype, site selectivity arises solely from different rates of epibatidine dissociation from the two sites. To determine the structural basis for epibatidine selectivity, we introduced mutations into either the gamma or the delta subunit and measured epibatidine binding and epibatidine-induced single-channel currents. Complexes formed by alpha and mutant gamma(K34S+F172I) subunits bind epibatidine with increased affinity compared to alphagamma complexes, whereas the kinetics of alpha2betadeltagamma(K34S+F172I) receptors reveal no change in affinity of the low-affinity site, but increased affinity of the high-affinity site. Conversely, complexes formed by alpha and mutant delta(S36K+I178F) subunits bind epibatidine with decreased affinity compared to alphadelta complexes, whereas the kinetics of alpha2betagammadelta(S36K+I178F) and alpha2betaepsilondelta(S36K+I178F) receptors show markedly reduced sensitivity to epibatidine. The overall data show that epibatidine activates muscle receptors by binding with high affinity to alphagamma and alphaepsilon sites, but with low affinity to the alphadelta site.

摘要

相似文献

1
Epibatidine activates muscle acetylcholine receptors with unique site selectivity.
Biophys J. 1998 Oct;75(4):1817-27. doi: 10.1016/S0006-3495(98)77623-4.
2
Epibatidine binds with unique site and state selectivity to muscle nicotinic acetylcholine receptors.
J Biol Chem. 1998 Apr 3;273(14):7843-9. doi: 10.1074/jbc.273.14.7843.
3
Structural basis for epibatidine selectivity at desensitized nicotinic receptors.
Mol Pharmacol. 2005 Jan;67(1):123-31. doi: 10.1124/mol.104.003665. Epub 2004 Oct 20.
4
Agonists binding nicotinic receptors elicit specific channel-opening patterns at αγ and αδ sites.
J Physiol. 2014 Jun 15;592(12):2501-17. doi: 10.1113/jphysiol.2013.267781. Epub 2014 Mar 24.
8
A fluorophore attached to nicotinic acetylcholine receptor beta M2 detects productive binding of agonist to the alpha delta site.
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10195-200. doi: 10.1073/pnas.0301885101. Epub 2004 Jun 24.
9
High affinity binding of epibatidine to serotonin type 3 receptors.
J Biol Chem. 2008 Apr 11;283(15):9659-65. doi: 10.1074/jbc.M703672200. Epub 2007 Aug 15.

引用本文的文献

3
Augmenting the antinociceptive effects of nicotinic acetylcholine receptor activity through lynx1 modulation.
PLoS One. 2018 Jul 3;13(7):e0199643. doi: 10.1371/journal.pone.0199643. eCollection 2018.
4
Agonists binding nicotinic receptors elicit specific channel-opening patterns at αγ and αδ sites.
J Physiol. 2014 Jun 15;592(12):2501-17. doi: 10.1113/jphysiol.2013.267781. Epub 2014 Mar 24.
5
Activation of heteroliganded mouse muscle nicotinic receptors.
J Physiol. 2005 Apr 15;564(Pt 2):359-76. doi: 10.1113/jphysiol.2004.078535. Epub 2005 Feb 17.
6
A fluorophore attached to nicotinic acetylcholine receptor beta M2 detects productive binding of agonist to the alpha delta site.
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10195-200. doi: 10.1073/pnas.0301885101. Epub 2004 Jun 24.
7
Activation and block of mouse muscle-type nicotinic receptors by tetraethylammonium.
J Physiol. 2003 Aug 15;551(Pt 1):155-68. doi: 10.1113/jphysiol.2003.043885. Epub 2003 Jun 24.
8
Tryptophan fluorescence reveals conformational changes in the acetylcholine binding protein.
J Biol Chem. 2002 Nov 1;277(44):41299-302. doi: 10.1074/jbc.C200462200. Epub 2002 Sep 13.
9
Mechanism of tacrine block at adult human muscle nicotinic acetylcholine receptors.
J Gen Physiol. 2002 Sep;120(3):369-93. doi: 10.1085/jgp.20028583.

本文引用的文献

1
Epibatidine binds with unique site and state selectivity to muscle nicotinic acetylcholine receptors.
J Biol Chem. 1998 Apr 3;273(14):7843-9. doi: 10.1074/jbc.273.14.7843.
3
The channel opening rate of adult- and fetal-type mouse muscle nicotinic receptors activated by acetylcholine.
J Physiol. 1998 Jan 1;506 ( Pt 1)(Pt 1):53-72. doi: 10.1111/j.1469-7793.1998.053bx.x.
5
Binding sites contribute unequally to the gating of mouse nicotinic alpha D200N acetylcholine receptors.
J Physiol. 1996 Oct 1;496 ( Pt 1)(Pt 1):185-96. doi: 10.1113/jphysiol.1996.sp021676.
7
Estimating single-channel kinetic parameters from idealized patch-clamp data containing missed events.
Biophys J. 1996 Jan;70(1):264-80. doi: 10.1016/S0006-3495(96)79568-1.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验