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目的:研究血脑屏障(BBB)上谷氨酸(Glu)外排是否受P-糖蛋白(P-gp)调节。方法:使用在体脑灌流技术,皮层内注射[~3H]Glu 5min,测定回收率,Glu单向转运常数(K_(in))和牛脑微血管内皮细胞(BCEC)及腔面膜摄取[~3H]Glu作用。结果:对照鼠,皮层内注射[~3H]Glu 5min回收率为25％±16％,先用环孢菌素A(CsA)10,100μmol·L~(-1),长春新碱(VCR)20μmol·L~(-1)和维拉帕米(Ver)100μmol·L~(-1)处理,回收率分别增至对照鼠的2.2,2.5,2.3和2.7倍。VCR和CsA增加[~3H]Glu K_(in)。CsA 40μmol·L~(-1)使[~3H]Glu在皮层、海马和纹状体中K_(in)值分别增至对照组的9,3,7和4.6倍。CsA 100μmol·L~(-1)使BCEC摄取[~3H]Glu增至对照组的2.5倍。MDR-逆转剂和P-gp单克隆抗体C_(219)抑制腔面膜摄取[~3H]Glu。结论:P-gp调节血脑屏障上的Glu外排。
AIM: To investigate whether glutamate (Glu) efflux in the blood-brain barrier (BBB) is regulated by P-glycoprotein (P-gp). Methods: The intracellular uptake of [~ 3H] Glu was measured by intracerebral perfusion. The recovery rate, Glu unidirectional transport constants (K_ (in)) and bovine brain microvascular endothelial cells Glu effect. Results: The recovery of [~ 3H] Glu in control group was 25% ± 16% after 5 h injection of corticosteroids. The control group was treated with cyclosporin A (CsA) 10,100μmol·L -1, VCR 20μmol · L -1 and 100 μmol·L -1 verapamil, the recoveries increased to 2.2, 2.5, 2.3 and 2.7 times of the control mice, respectively. VCR and CsA increase [~ 3H] Glu K_ (in). CsA at 40μmol·L -1 increased the K_ (in) values of [~ 3H] Glu in the cortex, hippocampus and striatum to 9, 3, 7 and 4.6 times of the control group, respectively. CsA 100 μmol·L -1 increased BCH uptake of [~ 3H] Glu to 2.5 times that of the control. MDR-reversal agent and P-gp monoclonal antibody C 219 can inhibit the uptake of [~ 3H] Glu in the luminal mucosa. Conclusion: P-gp regulates Glu efflux on the blood-brain barrier.