9-四氢大麻酚抑制茶碱与哺乳动物神经元和非神经元膜的结合。

delta-9-Tetrahydrocannabinol inhibits the binding of theophylline to mammalian neuronal and non-neuronal membranes.

作者信息

Ghosh S K, Poddar M K

机构信息

Department of Biochemistry, University College of Science, University of Calcutta, India.

出版信息

Biochem Pharmacol. 1993 Apr 22;45(8):1725-8. doi: 10.1016/0006-2952(93)90316-o.

DOI:10.1016/0006-2952(93)90316-o

PMID:8387304

Abstract

Theophylline (Th) (11.0 x 10(-6)-550.0 x 10(-6) M) shows dose dependent binding to the subcellular membranes of rat brain and liver. Its binding to neuronal membranes is in the order of synaptosome > microsome or mitochondrion > myelin. However, in the liver, Th binding to microsomes is greater than that to mitochondria. In all the membranes studied delta-9-tetrahydrocannabinol (THC) (1.6 x 10(-6)-13.33 x 10(-6) M) reduces the binding of Th. Scatchard plot analysis data suggest that this inhibitory effect of THC may arise from an allosteric change in the conformation of the Th binding sites not affecting the binding affinity of Th. Abrogation of the THC-induced inhibition of Th binding to control membranes after solubilization and restoration of the inhibitory effect of THC on Th binding in reconstituted membranes suggest the involvement of membrane lipid in the THC-induced inhibition of Th binding to neuronal and non-neuronal membranes.

摘要

茶碱（Th）（11.0×10⁻⁶ - 550.0×10⁻⁶ M）对大鼠脑和肝的亚细胞膜表现出剂量依赖性结合。它与神经细胞膜的结合顺序为突触体＞微粒体或线粒体＞髓磷脂。然而，在肝脏中，Th与微粒体的结合大于与线粒体的结合。在所研究的所有膜中，δ-9-四氢大麻酚（THC）（1.6×10⁻⁶ - 13.33×10⁻⁶ M）会降低Th的结合。Scatchard图分析数据表明，THC的这种抑制作用可能源于Th结合位点构象的变构变化，而不影响Th的结合亲和力。在溶解后消除THC诱导的对对照膜上Th结合的抑制作用，以及在重组膜中恢复THC对Th结合的抑制作用，表明膜脂参与了THC诱导的对神经和非神经细胞膜上Th结合的抑制作用。