Ito Y, Segawa K, Kobayashi M, Fukuda H
Department of Pharmacology, College of Pharmacy, Nihon University, Funabashi, Japan.
Neurochem Res. 1996 Aug;21(8):955-61. doi: 10.1007/BF02532346.
Zinc (Zn2+) was shown to invariably inhibit muscimol-stimulated 36Cl- uptake by synaptoneurosomes in the cerebral cortex, hippocampus and cerebellum. The Zn2+ sensitivity of the GABAA receptor-gated 36Cl- uptake in the cerebral cortex was comparable to that in the hippocampus, whereas the uptake in the cerebellum was less sensitive to Zn2+. Although diazepam-potentiation of muscimol-stimulated 36Cl- uptake was unaltered by 100 microM Zn2+ in the cerebral cortex and hippocampus, diazepam caused no enhancement in the presence of Zn2+ in the cerebellum. Zn2+ inhibited [3H]diazepam binding significantly at 1 mM in the cerebral cortex and cerebellum, whereas Ni2+ increased the binding in a concentration-dependent manner in both regions. Although lower concentrations of Zn2+ did not affect [3H]Ro 15-4513 binding to diazepam-sensitive sites, higher concentrations of ZN2+ increased the binding in both regions. Unlike the diazepam-sensitive sites, the diazepam-insensitive [3H]Ro 15-4513 binding was not affected by Zn2+ or Ni2+ at any of the tested concentrations. These results suggest that the GABAA ligand-gated Cl- flux and its diazepam-potentiation are heterogeneously modulated in various brain regions. It is also suggested that cerebellar diazepam-insensitive [3H]Ro 15-4513 binding sites are insensitive to Zn2+ and Ni2+.
锌（Zn2+）已被证明始终抑制大脑皮层、海马体和小脑中突触体神经小体对蝇蕈醇刺激的36Cl-摄取。大脑皮层中GABAA受体门控的36Cl-摄取对Zn2+的敏感性与海马体中的相当，而小脑中的摄取对Zn2+的敏感性较低。尽管在大脑皮层和海马体中，100 microM Zn2+不会改变地西泮对蝇蕈醇刺激的36Cl-摄取的增强作用，但在小脑中，存在Zn2+时地西泮不会增强这种作用。在大脑皮层和小脑中，1 mM的Zn2+显著抑制[3H]地西泮结合，而Ni2+在两个区域均以浓度依赖的方式增加结合。尽管较低浓度的Zn2+不影响[3H]Ro 15-4513与地西泮敏感位点的结合，但较高浓度的ZN2+在两个区域均增加结合。与地西泮敏感位点不同，在任何测试浓度下，地西泮不敏感的[3H]Ro 15-4513结合不受Zn2+或Ni2+影响。这些结果表明，GABAA配体门控的Cl-通量及其地西泮增强作用在不同脑区受到异质性调节。还表明，小脑地西泮不敏感的[3H]Ro 15-4513结合位点对Zn2+和Ni2+不敏感。
