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肌苷可能是培养的脊髓神经元上苯二氮䓬受体的内源性配体。

Inosine may be an endogenous ligand for benzodiazepine receptors on cultured spinal neurons.

作者信息

MacDonald J F, Barker J L, Paul S M, Marangos P J, Skolnick P

出版信息

Science. 1979 Aug 17;205(4407):715-7. doi: 10.1126/science.37602.

DOI:10.1126/science.37602
PMID:37602
Abstract

Mouse spinal neurons grown in tissue culture were used to study the membrane effects of the benzodiazepine flurazepam and the naturally occurring purine nucleoside inosine, which competes for benzodiazepine receptor sites in the central nervous system. Application of inosine elicited two types of transmitter-like membrane effects: a rapidly desensitizing excitatory response and a nondesensitizing inhibitory response. Flurazepam produced a similar excitatory response which showed cross-desensitization with the purine excitation. Flurazepam also blocked the inhibitory inosine response. The results provide electrophysiological evidence that an endogenous purine can activate two different conductances on spinal neurons and that flurazepam can activate one of the conductances and antagonize the other.

摘要

在组织培养中生长的小鼠脊髓神经元被用于研究苯二氮䓬类药物氟西泮和天然存在的嘌呤核苷肌苷对膜的影响,肌苷在中枢神经系统中与苯二氮䓬受体位点竞争。应用肌苷引发了两种类似递质的膜效应:一种快速脱敏的兴奋性反应和一种非脱敏的抑制性反应。氟西泮产生了类似的兴奋性反应,该反应与嘌呤激发表现出交叉脱敏。氟西泮还阻断了肌苷的抑制性反应。这些结果提供了电生理证据,即内源性嘌呤可以激活脊髓神经元上两种不同的电导,并且氟西泮可以激活其中一种电导并拮抗另一种电导。

相似文献

1
Inosine may be an endogenous ligand for benzodiazepine receptors on cultured spinal neurons.肌苷可能是培养的脊髓神经元上苯二氮䓬受体的内源性配体。
Science. 1979 Aug 17;205(4407):715-7. doi: 10.1126/science.37602.
2
Purines as endogenous ligands of the benzodiazepine receptor.
Fed Proc. 1980 Oct;39(12):3050-55.
3
Identification of inosine and hypoxanthine as endogenous ligands for the brain benzodiazepine-binding sites.肌苷和次黄嘌呤作为脑内苯二氮䓬结合位点内源性配体的鉴定。
Proc Natl Acad Sci U S A. 1979 Feb;76(2):977-81. doi: 10.1073/pnas.76.2.977.
4
The benzodiazepines and inosine antagonize caffeine-induced seizures.苯二氮卓类药物和肌苷可拮抗咖啡因诱发的癫痫发作。
Psychopharmacology (Berl). 1981;72(3):269-73. doi: 10.1007/BF00431829.
5
Inosine, an endogenous ligand of the brain benzodiazepine receptor, antagonizes pentylenetetrazole-evoked seizures.肌苷是脑苯二氮䓬受体的内源性配体,可拮抗戊四氮诱发的癫痫发作。
Proc Natl Acad Sci U S A. 1979 Mar;76(3):1515-8. doi: 10.1073/pnas.76.3.1515.
6
Characterization of benzodiazepine receptors in primary cultures of fetal mouse brain and spinal cord neurons.
Brain Res. 1980 May 26;190(2):485-91. doi: 10.1016/0006-8993(80)90290-5.
7
Multiple actions of picomolar concentrations of flurazepam on the excitability of cultured mouse spinal neurons.皮摩尔浓度的氟西泮对培养的小鼠脊髓神经元兴奋性的多种作用。
Brain Res. 1982 Aug 26;246(2):257-64. doi: 10.1016/0006-8993(82)91173-8.
8
Identification of inosine as an endogenous modulator for the benzodiazepine binding site of the GABAA receptors.鉴定肌苷作为γ-氨基丁酸A受体苯二氮䓬结合位点的内源性调节剂。
J Biomed Sci. 1998 Jul-Aug;5(4):274-80. doi: 10.1007/BF02255859.
9
Benzodiazepine receptor: localization by photoaffinity labeling and isolation of a possible endogenous ligand.苯二氮䓬受体:通过光亲和标记进行定位并分离出一种可能的内源性配体。
Adv Biochem Psychopharmacol. 1980;21:295-9.
10
Chronic flurazepam treatment produces decreased efficacy of the benzodiazepine ligands and pentobarbital with gamma-aminobutyric acidA receptors in cortical neurons.长期氟西泮治疗会降低苯二氮䓬类配体和戊巴比妥与皮质神经元中γ-氨基丁酸A受体的结合效率。
J Pharmacol Exp Ther. 1994 Aug;270(2):485-90.

引用本文的文献

1
Light-Activated Agonist-Potentiator of GABA Receptors for Reversible Neuroinhibition in Wildtype Mice.用于野生型小鼠可逆神经抑制的光激活 GABA 受体激动剂增效剂。
J Am Chem Soc. 2024 Oct 23;146(42):28822-28831. doi: 10.1021/jacs.4c08446. Epub 2024 Oct 9.
2
Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?肌苷作为理解和治疗中枢神经系统疾病的工具:一个被忽视的角色?
Front Neurosci. 2021 Aug 24;15:703783. doi: 10.3389/fnins.2021.703783. eCollection 2021.
3
Theophylline inhibition of renal and cerebral nucleoside formation.
茶碱对肾脏和大脑核苷形成的抑制作用。
Br J Pharmacol. 1981 Jun;73(2):467-9. doi: 10.1111/j.1476-5381.1981.tb10444.x.
4
The benzodiazepines and inosine antagonize caffeine-induced seizures.苯二氮卓类药物和肌苷可拮抗咖啡因诱发的癫痫发作。
Psychopharmacology (Berl). 1981;72(3):269-73. doi: 10.1007/BF00431829.
5
Anticonvulsant doses of inosine result in brain levels sufficient to inhibit [3H] diazepam binding.
Psychopharmacology (Berl). 1981;75(2):175-8. doi: 10.1007/BF00432183.
6
Biomolecular information analysis in neurotransmitter systems.神经递质系统中的生物分子信息分析
Acta Biotheor. 1984;33(1):3-33. doi: 10.1007/BF00045844.
7
Purification and characterization of a benzodiazepine-like substance from mammalian brain.从哺乳动物大脑中提纯并鉴定一种苯二氮卓类物质。
Neurochem Res. 1989 Apr;14(4):345-52. doi: 10.1007/BF01000037.