是什么赋予了甘氨酸与它的受体位点结合的特异性？
What confers specificity on glycine for its receptor site?
作者信息
Tokutomi N, Kaneda M, Akaike N
机构信息
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
出版信息
Br J Pharmacol. 1989 Jun;97(2):353-60. doi: 10.1111/j.1476-5381.1989.tb11961.x.
Abstract
- The structural requirements for activation of the glycine receptor were studied in isolated ventromedial hypothalamic neurones of rats by use of a 'concentration-clamp' technique under single-electrode voltage-clamp conditions. 2. alpha-Amino acids (L-alpha-alanine, and D-alpha-alanine, and L-serine), and glycine-methylester, glycine-ethylester and beta-amino acids (beta-alanine and taurine) produced a transient inward Cl- current, which was similar to that induced by glycine. 3. The responses to individual alpha- and beta-amino acids were selectively antagonized by strychnine, but were not affected by bicuculline, picrotoxin or the taurine antagonist, TAG (6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1,1-dioxide hydrochloride), suggesting that alpha- and beta-amino acids activate the same glycine receptor. 4. beta-Amino acids were slightly more potent than the alpha-amino acids in causing cross-desensitization of the glycine response. 5. From the results of the structure-activity analysis of the optical isomers of alpha-alanine, serine and cysteine, a tentative structure of the glycine receptor is proposed.
摘要
- 采用“浓度钳”技术，在单电极电压钳条件下，对大鼠离体下丘脑腹内侧神经元中甘氨酸受体激活的结构要求进行了研究。2. α-氨基酸（L-α-丙氨酸、D-α-丙氨酸和L-丝氨酸）、甘氨酸甲酯、甘氨酸乙酯和β-氨基酸（β-丙氨酸和牛磺酸）产生瞬时内向Cl⁻电流，这与甘氨酸诱导的电流相似。3. 士的宁可选择性拮抗对单个α-和β-氨基酸的反应，但不受荷包牡丹碱、苦味毒或牛磺酸拮抗剂TAG（6-氨甲基-3-甲基-4H,1,2,4-苯并噻二嗪-1,1-二氧化物盐酸盐）的影响，这表明α-和β-氨基酸激活相同的甘氨酸受体。4. β-氨基酸在引起甘氨酸反应的交叉脱敏方面比α-氨基酸稍强。5. 根据对α-丙氨酸、丝氨酸和半胱氨酸光学异构体的构效分析结果，提出了甘氨酸受体的初步结构。
相似文献
1
What confers specificity on glycine for its receptor site?是什么赋予了甘氨酸与它的受体位点结合的特异性？
Br J Pharmacol. 1989 Jun;97(2):353-60. doi: 10.1111/j.1476-5381.1989.tb11961.x.
2
Comparison of the actions of glycine and related amino acids on isolated third order neurons from the tiger salamander retina.
Neuroscience. 1995 Jan;64(1):153-64. doi: 10.1016/0306-4522(94)00399-p.
3
Glycine-related amino acids stereoselectively affect N-methyl-D-aspartate receptor-mediated contractions of guinea pig ileum: comparison with the inhibition of strychnine-insensitive [3H]glycine binding to rat cortical membranes.甘氨酸相关氨基酸对豚鼠回肠中N-甲基-D-天冬氨酸受体介导的收缩产生立体选择性影响：与对大鼠皮层膜上士的宁不敏感的[3H]甘氨酸结合抑制作用的比较。
Neuropharmacology. 1990 Feb;29(2):145-50. doi: 10.1016/0028-3908(90)90054-u.
4
Studies on convulsants in the isolated frog spinal cord. I. Antagonism of amino acid responses.离体蛙脊髓中惊厥剂的研究。I. 氨基酸反应的拮抗作用。
J Physiol. 1975 Mar;245(3):521-36. doi: 10.1113/jphysiol.1975.sp010859.
5
Cycloleucine blocks NMDA responses in cultured hippocampal neurones under voltage clamp: antagonism at the strychnine-insensitive glycine receptor.在电压钳制下，环亮氨酸可阻断培养的海马神经元中的NMDA反应：对士的宁不敏感的甘氨酸受体具有拮抗作用。
Br J Pharmacol. 1989 Nov;98(3):1005-13. doi: 10.1111/j.1476-5381.1989.tb14632.x.
6
Effects of the beta-amino acid antagonist TAG on thalamocortical inhibition.β-氨基酸拮抗剂TAG对丘脑皮质抑制的影响。
Neuropharmacology. 2009 Jun;56(8):1097-105. doi: 10.1016/j.neuropharm.2009.03.008. Epub 2009 Mar 28.
7
8
beta-Alanine and taurine microinjected into the rat caudal ventrolateral medulla increase blood pressure.
Clin Exp Hypertens. 1993 May;15(3):585-97. doi: 10.3109/10641969309041631.
9
L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons.L-脯氨酸激活培养的大鼠背根神经节神经元中的谷氨酸和甘氨酸受体。
Mol Pharmacol. 1992 Apr;41(4):793-801.
10
Taurine activates excitatory non-synaptic glycine receptors on dopamine neurones in ventral tegmental area of young rats.牛磺酸可激活幼鼠腹侧被盖区多巴胺神经元上的兴奋性非突触甘氨酸受体。
J Physiol. 2005 Jun 1;565(Pt 2):503-16. doi: 10.1113/jphysiol.2005.085423. Epub 2005 Apr 7.
引用本文的文献
1
A Structural Rationale for N-Methylbicuculline Acting as a Promiscuous Competitive Antagonist of Inhibitory Pentameric Ligand-Gated Ion Channels.N-甲基荷包牡丹碱作为抑制性五聚体配体门控离子通道的非选择性竞争性拮抗剂的结构基础。
Chembiochem. 2020 May 15;21(10):1526-1533. doi: 10.1002/cbic.201900680. Epub 2020 Feb 12.
2
Diverse small molecules prevent macrophage lysis during pyroptosis.多种小分子可防止细胞焦亡时巨噬细胞的裂解。
Cell Death Dis. 2019 Apr 11;10(4):326. doi: 10.1038/s41419-019-1559-4.
3
The role of glycine in regulated cell death.甘氨酸在程序性细胞死亡中的作用。
Cell Mol Life Sci. 2016 Jun;73(11-12):2285-308. doi: 10.1007/s00018-016-2201-6. Epub 2016 Apr 11.
4
Activation of glycine and extrasynaptic GABA(A) receptors by taurine on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis.牛磺酸对三叉神经尾侧亚核胶状质神经元甘氨酸和突触外GABA(A)受体的激活作用。
Neural Plast. 2013;2013:740581. doi: 10.1155/2013/740581. Epub 2013 Nov 28.
5
Taurine activates excitatory non-synaptic glycine receptors on dopamine neurones in ventral tegmental area of young rats.牛磺酸可激活幼鼠腹侧被盖区多巴胺神经元上的兴奋性非突触甘氨酸受体。
J Physiol. 2005 Jun 1;565(Pt 2):503-16. doi: 10.1113/jphysiol.2005.085423. Epub 2005 Apr 7.
6
Beta-alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro.β-丙氨酸和牛磺酸作为大鼠海马体中甘氨酸受体的内源性激动剂（体外实验）。
J Physiol. 2002 Feb 15;539(Pt 1):191-200. doi: 10.1113/jphysiol.2001.013147.
7
Actions of 3-[2-phosphonomethyl[1,1-biphenyl]-3-yl]alanine (PMBA) on cloned glycine receptors.3-[2-膦酰甲基[1,1-联苯]-3-基]丙氨酸（PMBA）对克隆甘氨酸受体的作用。
Br J Pharmacol. 1999 Mar;126(5):1230-6. doi: 10.1038/sj.bjp.0702402.
8
Glycine receptors in cultured chick sympathetic neurons are excitatory and trigger neurotransmitter release.培养的鸡交感神经元中的甘氨酸受体具有兴奋性并触发神经递质释放。
J Physiol. 1997 Nov 1;504 ( Pt 3)(Pt 3):683-94. doi: 10.1111/j.1469-7793.1997.683bd.x.
9
Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation.牛磺酸对大鼠视上核大细胞神经元甘氨酸受体的激动作用：在渗透调节中的可能作用。
J Physiol. 1997 Aug 1;502 ( Pt 3)(Pt 3):609-21. doi: 10.1111/j.1469-7793.1997.609bj.x.
10
Patch-clamp analysis of glycine-induced currents in chick ciliary ganglion neurons.鸡睫状神经节神经元中甘氨酸诱导电流的膜片钳分析
J Physiol. 1995 Sep 1;487 ( Pt 2)(Pt 2):395-405. doi: 10.1113/jphysiol.1995.sp020888.
本文引用的文献
1
Further evidence for selective antagonism of taurine by 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide.6-氨甲基-3-甲基-4H-1,2,4-苯并噻二嗪-1,1-二氧化物对牛磺酸选择性拮抗作用的进一步证据。
Brain Res. 1981 Dec 21;229(2):530-5. doi: 10.1016/0006-8993(81)91017-9.
2
Neuropharmacological characterization of a taurine antagonist.一种牛磺酸拮抗剂的神经药理学特性
J Pharmacol Exp Ther. 1981 Dec;219(3):604-13.
3
Internal perfusion studies demonstrating GABA-induced chloride responses in frog primary afferent neurons.体内灌注研究表明，γ-氨基丁酸（GABA）可诱导青蛙初级传入神经元产生氯离子反应。
Am J Physiol. 1984 Mar;246(3 Pt 1):C259-65. doi: 10.1152/ajpcell.1984.246.3.C259.
4
Separation of ionic currents in the somatic membrane of frog sensory neurons.青蛙感觉神经元胞体膜中离子电流的分离
J Membr Biol. 1984;78(1):19-28. doi: 10.1007/BF01872528.
5
Determination of the equilibrium dissociation constants and number of glycine binding sites in several areas of the rat central nervous system, using a sodium-independent system.使用不依赖钠离子的系统测定大鼠中枢神经系统多个区域中甘氨酸结合位点的平衡解离常数和数量。
J Neurochem. 1981 Oct;37(4):1015-24. doi: 10.1111/j.1471-4159.1981.tb04489.x.
6
Localization of high affinity [3H]glycine transport sites in the cerebellar cortex.
Brain Res. 1981 Jul 6;216(1):11-33. doi: 10.1016/0006-8993(81)91275-0.
7
Evidence for taurine as an inhibitory neurotransmitter in cerebellar stellate interneurons: selective antagonism by TAG (6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1,1-dioxide).牛磺酸作为小脑星状中间神经元中抑制性神经递质的证据：TAG（6-氨基甲基-3-甲基-4H,1,2,4-苯并噻二嗪-1,1-二氧化物）的选择性拮抗作用。
Brain Res. 1983 Apr 11;265(1):163-8. doi: 10.1016/0006-8993(83)91350-1.
8
The status of glycine as a supraspinal neurotransmitter.甘氨酸作为脊髓上神经递质的地位。
Life Sci. 1981 Jun 15;28(24):2679-86. doi: 10.1016/0024-3205(81)90168-5.
9
A pharmacological study of the depression of spinal neurones by glycine and related amino acids.甘氨酸及相关氨基酸对脊髓神经元抑制作用的药理学研究。
Exp Brain Res. 1968;6(1):1-18. doi: 10.1007/BF00235443.
10
Glycine uptake in rat central nervous system slices and homogenates: evidence for different uptake systems in spinal cord and cerebral cortex.大鼠中枢神经系统切片和匀浆中的甘氨酸摄取：脊髓和大脑皮层中不同摄取系统的证据。
J Neurochem. 1971 Oct;18(10):1951-61. doi: 10.1111/j.1471-4159.1971.tb09601.x.
Zotero 插件