Peris J
Dept. Pharmacodynamics, University of Florida Health Sciences Center, Gainesville 32610.
Life Sci. 1993;53(9):707-15. doi: 10.1016/0024-3205(93)90247-z.
Marked regional differences in the mRNA levels for the different subunits of the GABAA receptor may result in functional differences throughout the brain. The effects of different GABAA agonists and antagonists on GABAA receptor function was measured using 36Cl- uptake in microsacs made from cerebellum (CB), superior colliculus (SC), substantia nigra (SN), inferior colliculus (IC) or cortex (CT) containing equal amounts of protein. GABA increased Cl- uptake in all regions in a dose-dependent and saturable manner but with markedly different efficacies across brain regions. Maximal GABA-stimulated uptake was 59 +/- 2 nmoles of Cl- per mg protein in CT, 25 +/- 5 in SC, 24 +/- 4 in CB, 16 +/- 1 in IC and 6.7 +/- 1.4 in SN. Muscimol increased Cl- uptake with greater potency than GABA but with similar efficacies in CT, CB, SC and SN; the efficacy of muscimol in IC was increased to 27.4 +/- 5. Picrotoxin inhibited maximal GABA-stimulated Cl- uptake in CB, SC and CT but did not decrease uptake in IC or SN. Bicuculline methiodide completely inhibited uptake in CB and CT, partially inhibited uptake in IC, and did not affect uptake in SC and SN. These data provide functional support for regional heterogeneity of the GABAA receptor/Cl- ionophore between nigrocollicular regions and CB and CT.
GABAA受体不同亚基的mRNA水平存在显著的区域差异，这可能导致整个大脑的功能差异。使用来自小脑（CB）、上丘（SC）、黑质（SN）、下丘（IC）或皮层（CT）且含有等量蛋白质的微囊，通过³⁶Cl摄取来测量不同GABAA激动剂和拮抗剂对GABAA受体功能的影响。GABA以剂量依赖性和饱和性方式增加所有区域的Cl⁻摄取，但在不同脑区的效力明显不同。GABA刺激的最大摄取量在CT中为每毫克蛋白质59±2纳摩尔Cl⁻，在SC中为25±5，在CB中为24±4，在IC中为16±1，在SN中为6.7±1.4。蝇蕈醇增加Cl⁻摄取的效力比GABA更强，但在CT、CB、SC和SN中的效力相似；蝇蕈醇在IC中的效力增加到27.4±5。印防己毒素抑制CB、SC和CT中GABA刺激的最大Cl⁻摄取，但不降低IC或SN中的摄取。荷包牡丹碱甲碘化物完全抑制CB和CT中的摄取，部分抑制IC中的摄取，且不影响SC和SN中的摄取。这些数据为黑质 - 丘系区域与CB和CT之间GABAA受体/Cl⁻离子载体的区域异质性提供了功能支持。
