Peris J, Shawley A, Dawson R, Abendschein K H
Dept. of Pharmacodynamics, University of Florida Health Science Center, Gainesville 32610.
Life Sci. 1991;49(11):PL49-54. doi: 10.1016/0024-3205(91)90250-f.
The allosteric regulation of specific 35S-TBPS binding to the convulsant site on the GABAA receptor/chloride (Cl-) ionophore complex was studied in various brain regions in an attempt to characterize regional heterogeneity of the protein subunits forming the complex. Bicuculline methiodide (BIC), a GABAA antagonist, enhanced binding in cortex (CTX), substantia nigra (SN) and cerebellum (CBL), inhibited binding in inferior colliculus (IC) and did not affect binding in superior colliculus (SC). Similar results were found in CBL and IC using SR-95531, another GABAA antagonist. The levels of endogenous GABA in the different tissue samples could not account for the regional differences in binding. When the functional regulation of these receptors was measured using 36Cl- uptake in microsomes, muscimol-stimulated uptake was completely blocked by BIC in CBL and IC but was not affected by BIC in SC. Additionally, picrotoxin completely blocked muscimol-stimulated uptake in CBL but had no effect in IC or SC. These findings provide a functional basis for regional heterogeneity of GABAA receptor.
研究了特异性35S-TBPS与GABAA受体/氯离子（Cl-）离子载体复合物上惊厥位点结合的变构调节，以试图表征构成该复合物的蛋白质亚基的区域异质性。GABAA拮抗剂荷包牡丹碱甲碘化物（BIC）增强了皮质（CTX）、黑质（SN）和小脑（CBL）中的结合，抑制了下丘（IC）中的结合，并且不影响上丘（SC）中的结合。使用另一种GABAA拮抗剂SR-95531在CBL和IC中发现了类似结果。不同组织样品中内源性GABA的水平不能解释结合的区域差异。当使用微粒体中的36Cl-摄取来测量这些受体的功能调节时，在CBL和IC中，蝇蕈醇刺激的摄取被BIC完全阻断，但在SC中不受BIC影响。此外，印防己毒素完全阻断了CBL中蝇蕈醇刺激的摄取，但对IC或SC没有影响。这些发现为GABAA受体的区域异质性提供了功能基础。
