苯甘氨酸衍生物作为新生大鼠初级传入神经末梢上表达的III型代谢型谷氨酸受体的拮抗剂。
Phenylglycine derivatives as antagonists of group III metabotropic glutamate receptors expressed on neonatal rat primary afferent terminals.
作者信息
Miller Jacqueline C, Howson Patrick A, Conway Stuart J, Williams Richard V, Clark Barry P, Jane David E
机构信息
Department of Pharmacology, School of Medical Sciences, Bristol BS8 1TD. Eli Lilly and Co., Erl Wood Manor, Windlesham, Surrey GU20 6PH.
出版信息
Br J Pharmacol. 2003 Aug;139(8):1523-31. doi: 10.1038/sj.bjp.0705377.
Abstract
- Three novel phenylglycine analogues; (RS)-alpha-methyl-3-chloro-4-phosphonophenylglycine (UBP1110), (RS)-alpha-methyl-3-methoxy-4-phosphonophenylglycine (UBP1111) and (RS)-alpha-methyl-3-methyl-4-phosphonophenylglycine (UBP1112) antagonised the depression of the fast component of the dorsal root-evoked ventral root potential induced by (S)-AP4 with apparent K(D) values of: 7.4+/-2.3, 5.4+/-0.6 and 5.1+/-0.3 micro M (all n=3), respectively. 2. A Schild analysis of the antagonism of (S)-AP4 induced depression of synaptic transmission by UBP1112 revealed a pA(2) value of 5.3 and a slope of 0.81+/-0.26 (n=9). 3. None of the phenylglycines tested were potent antagonists of responses mediated by group II mGlu receptors (apparent K(D) values >480 micro M). UBP1112 when tested at a concentration of 1 mM had little or no activity on (S)-3,5-DHPG-, NMDA-, AMPA- or kainate-induced responses on motoneurones. 4. UBP1110, UBP1111 and UBP1112 are at least 100-fold selective for group III over group I and II mGlu receptors expressed in the spinal cord making them the most potent, selective, antagonists yet tested at (S)-AP4 sensitive receptors in the spinal cord.
摘要
- 三种新型苯甘氨酸类似物：（RS）-α-甲基-3-氯-4-膦酰基苯甘氨酸（UBP1110）、（RS）-α-甲基-3-甲氧基-4-膦酰基苯甘氨酸（UBP1111）和（RS）-α-甲基-3-甲基-4-膦酰基苯甘氨酸（UBP1112）拮抗了由（S）-AP4诱导的背根诱发腹根电位快速成分的抑制，其表观解离常数（KD）值分别为：7.4±2.3、5.4±0.6和5.1±0.3 μM（均为n = 3）。2. 对UBP1112拮抗（S）-AP4诱导的突触传递抑制作用进行的希尔德分析显示，其pA2值为5.3，斜率为0.81±0.26（n = 9）。3. 所测试的苯甘氨酸均不是II组代谢型谷氨酸受体介导反应的强效拮抗剂（表观KD值>480 μM）。当以1 mM的浓度进行测试时，UBP1112对运动神经元上由（S）-3,5-二羟基苯甘氨酸、N-甲基-D-天冬氨酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸或海人藻酸诱导的反应几乎没有活性。4. UBP1110、UBP1111和UBP1112对脊髓中表达的III组代谢型谷氨酸受体的选择性比对I组和II组代谢型谷氨酸受体至少高100倍，这使得它们成为在脊髓中对（S）-AP4敏感受体进行测试的最有效、选择性最强的拮抗剂。
相似文献
1
Phenylglycine derivatives as antagonists of group III metabotropic glutamate receptors expressed on neonatal rat primary afferent terminals.苯甘氨酸衍生物作为新生大鼠初级传入神经末梢上表达的III型代谢型谷氨酸受体的拮抗剂。
Br J Pharmacol. 2003 Aug;139(8):1523-31. doi: 10.1038/sj.bjp.0705377.
2
(S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord.（S）-3,4-二氯苯基甘氨酸，一种强效且选择性的代谢型谷氨酸受体8a（mGlu8a）激动剂，可激活新生大鼠脊髓初级传入终末上的代谢型谷氨酸受体。
Neuropharmacology. 2001 Mar;40(3):311-8. doi: 10.1016/s0028-3908(00)00169-6.
3
Potent antagonists at the L-AP4- and (1S,3S)-ACPD-sensitive presynaptic metabotropic glutamate receptors in the neonatal rat spinal cord.新生大鼠脊髓中对L-AP4和（1S，3S）-ACPD敏感的突触前代谢型谷氨酸受体的强效拮抗剂。
Neuropharmacology. 1996;35(8):1029-35. doi: 10.1016/s0028-3908(96)00048-2.
4
Dual modulation of excitatory synaptic transmission by agonists at group I metabotropic glutamate receptors in the rat spinal dorsal horn.大鼠脊髓背角中I组代谢型谷氨酸受体激动剂对兴奋性突触传递的双重调节
Brain Res. 2000 Dec 29;887(2):359-77. doi: 10.1016/s0006-8993(00)03066-3.
5
Synthesis of phenylglycine derivatives as potent and selective antagonists of group III metabotropic glutamate receptors.苯甘氨酸衍生物作为Ⅲ型代谢型谷氨酸受体强效选择性拮抗剂的合成
Bioorg Med Chem Lett. 2001 Mar 26;11(6):777-80. doi: 10.1016/s0960-894x(01)00052-x.
6
The novel antagonist 3-CBW discriminates between kainate receptors expressed on neonatal rat motoneurones and those on dorsal root C-fibres.新型拮抗剂3-CBW能够区分新生大鼠运动神经元上表达的海人酸受体和背根C纤维上的海人酸受体。
Br J Pharmacol. 2002 Dec;137(7):1125-33. doi: 10.1038/sj.bjp.0704957.
7
Pharmacological differentiation of kainate receptors on neonatal rat spinal motoneurones and dorsal roots.新生大鼠脊髓运动神经元和背根上红藻氨酸受体的药理学差异
Neuropharmacology. 1998 Oct-Nov;37(10-11):1223-37. doi: 10.1016/s0028-3908(98)00124-5.
8
Group II and group III metabotropic glutamate receptor agonists depress synaptic transmission in the rat spinal cord dorsal horn.第二组和第三组代谢型谷氨酸受体激动剂可抑制大鼠脊髓背角的突触传递。
Neuroscience. 2000;100(2):393-406. doi: 10.1016/s0306-4522(00)00269-4.
9
New phenylglycine derivatives with potent and selective antagonist activity at presynaptic glutamate receptors in neonatal rat spinal cord.在新生大鼠脊髓中对突触前谷氨酸受体具有强效和选择性拮抗活性的新型苯甘氨酸衍生物。
Neuropharmacology. 1995 Aug;34(8):851-6. doi: 10.1016/0028-3908(95)00063-c.
10
Differential roles of mGlu8 receptors in the regulation of glutamate and gamma-aminobutyric acid release at periaqueductal grey level.代谢型谷氨酸受体8在中脑导水管周围灰质水平调节谷氨酸和γ-氨基丁酸释放中的不同作用。
Neuropharmacology. 2005;49 Suppl 1:157-66. doi: 10.1016/j.neuropharm.2005.02.006. Epub 2005 Apr 1.
引用本文的文献
1
Group III metabotropic glutamate receptors gate long-term potentiation and synaptic tagging/capture in rat hippocampal area CA2.III 型代谢型谷氨酸受体控制大鼠海马 CA2 区的长时程增强和突触标记/捕获。
Elife. 2020 Apr 20;9:e55344. doi: 10.7554/eLife.55344.
2
Group III metabotropic glutamate receptors: pharmacology, physiology and therapeutic potential.Ⅲ组代谢型谷氨酸受体：药理学、生理学及治疗潜力
Neurochem Res. 2014 Oct;39(10):1876-94. doi: 10.1007/s11064-014-1415-y. Epub 2014 Aug 22.
3
Independent presynaptic and postsynaptic mechanisms regulate endocannabinoid signaling at multiple synapses in the ventral tegmental area.独立的突触前和突触后机制调节腹侧被盖区多个突触处的内源性大麻素信号传导。
J Neurosci. 2004 Dec 8;24(49):11070-8. doi: 10.1523/JNEUROSCI.3695-04.2004.
本文引用的文献
1
Actions of LY341495 on metabotropic glutamate receptor-mediated responses in the neonatal rat spinal cord.LY341495对新生大鼠脊髓中代谢型谷氨酸受体介导反应的作用
Br J Pharmacol. 2003 May;139(1):147-55. doi: 10.1038/sj.bjp.0705230.
2
Role of group II and group III metabotropic glutamate receptors in spinal cord injury.II 型和 III 型代谢型谷氨酸受体在脊髓损伤中的作用。
Exp Neurol. 2002 Jan;173(1):153-67. doi: 10.1006/exnr.2001.7828.
3
Developmental regulation of N-methyl-D-aspartate- and kainate-type glutamate receptor expression in the rat spinal cord.大鼠脊髓中N-甲基-D-天冬氨酸型和红藻氨酸型谷氨酸受体表达的发育调控
Neuroscience. 2001;105(2):499-507. doi: 10.1016/s0306-4522(01)00143-9.
4
Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system.揭示中枢神经系统中突触前代谢型谷氨酸受体的功能。
J Pharmacol Exp Ther. 2001 Oct;299(1):12-20.
5
Anticonvulsant activity of 3,4-dicarboxyphenylglycines in DBA/2 mice.
Neuropharmacology. 2001 Apr;40(5):732-5. doi: 10.1016/s0028-3908(01)00002-8.
6
Synthesis of phenylglycine derivatives as potent and selective antagonists of group III metabotropic glutamate receptors.苯甘氨酸衍生物作为Ⅲ型代谢型谷氨酸受体强效选择性拮抗剂的合成
Bioorg Med Chem Lett. 2001 Mar 26;11(6):777-80. doi: 10.1016/s0960-894x(01)00052-x.
7
Immunoreactivity for the group III metabotropic glutamate receptor subtype mGluR4a in the superficial laminae of the rat spinal dorsal horn.
J Comp Neurol. 2001 Feb 19;430(4):448-57. doi: 10.1002/1096-9861(20010219)430:4<448::aid-cne1042>3.0.co;2-o.
8
(S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord.（S）-3,4-二氯苯基甘氨酸，一种强效且选择性的代谢型谷氨酸受体8a（mGlu8a）激动剂，可激活新生大鼠脊髓初级传入终末上的代谢型谷氨酸受体。
Neuropharmacology. 2001 Mar;40(3):311-8. doi: 10.1016/s0028-3908(00)00169-6.
9
Binding of [3H](2S,1'S,2'S)-2-(9-xanthylmethyl)-2-(2'-carboxycyclopropyl) glycine ([3H]LY341495) to cell membranes expressing recombinant human group III metabotropic glutamate receptor subtypes.[3H](2S,1'S,2'S)-2-(9-呫吨基甲基)-2-(2'-羧基环丙基)甘氨酸([3H]LY341495)与表达重组人III型代谢型谷氨酸受体亚型的细胞膜的结合。
Naunyn Schmiedebergs Arch Pharmacol. 2000 Dec;362(6):546-54. doi: 10.1007/s002100000305.
10
Regulation of neurotransmitter release by metabotropic glutamate receptors.代谢型谷氨酸受体对神经递质释放的调节。
J Neurochem. 2000 Sep;75(3):889-907. doi: 10.1046/j.1471-4159.2000.0750889.x.
Zotero 插件