Kawai N, Yamamoto T, Yamamoto H, McCarron R M, Spatz M
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
J Neurochem. 1995 Oct;65(4):1588-96. doi: 10.1046/j.1471-4159.1995.65041588.x.
The effect of endothelins (ET-1 and ET-3) on 86Rb+ uptake as a measure of K+ uptake was investigated in cultured rat brain capillary endothelium. ET-1 or ET-3 dose-dependently enhanced K+ uptake (EC50 = 0.60 +/- 0.15 and 21.5 +/- 4.1 nM, respectively), which was inhibited by the selective ETA receptor antagonist BQ 123 (cyclo-D-Trp-D-Asp-Pro-D-Val-Leu). Neither the selective ETB agonists IRL 1620 [N-succinyl-(Glu9,-Ala11,15)-ET-1] and sarafotoxin S6c, nor the ETB receptor antagonist IRL 1038 [(Cys11,Cys15)-ET-1] had any effect on K+ uptake. Ouabain (inhibitor of Na+,K(+)-ATPase) and bumetanide (inhibitor of Na(+)-K(+)-Cl- cotransport) reduced (up to 40% and up to 70%, respectively) the ET-1-stimulated K+ uptake. Complete inhibition was seen with both agents. Phorbol 12-myristate 13-acetate (PMA), activator of protein kinase C (PKC), stimulated Na+,K(+)-ATPase and Na(+)-K(+)-Cl- cotransport. ET-1- but not PMA-stimulated K+ uptake was inhibited by 5-(N-ethyl-N-isopropyl)amiloride (inhibitor of Na+/H+ exchange system), suggesting a linkage of Na+/H+ exchange with ET-1-stimulated Na+,K(+)-ATPase and Na(+)-K(+)-Cl- cotransport activity that is not mediated by PKC.
在内皮素（ET-1和ET-3）对86Rb+摄取作为钾离子摄取指标的影响的研究中，使用了培养的大鼠脑毛细血管内皮细胞。ET-1或ET-3呈剂量依赖性地增强钾离子摄取（EC50分别为0.60±0.15和21.5±4.1 nM），这一作用被选择性ETA受体拮抗剂BQ 123（环-D-色氨酸-D-天冬氨酸-脯氨酸-D-缬氨酸-亮氨酸）所抑制。选择性ETB激动剂IRL 1620 [N-琥珀酰-（Glu9，-Ala11,15）-ET-1]和铃蟾毒素S6c，以及ETB受体拮抗剂IRL 1038 [（Cys11，Cys15）-ET-1]对钾离子摄取均无影响。哇巴因（钠钾ATP酶抑制剂）和布美他尼（钠钾氯协同转运抑制剂）分别使ET-1刺激的钾离子摄取降低（分别高达40%和70%）。两种药物共同作用时可见完全抑制。蛋白激酶C（PKC）激活剂佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）刺激钠钾ATP酶和钠钾氯协同转运。5-（N-乙基-N-异丙基）氨氯吡咪（钠氢交换系统抑制剂）抑制ET-1刺激的而非PMA刺激的钾离子摄取，提示钠氢交换与ET-1刺激的钠钾ATP酶和钠钾氯协同转运活性相关，且该联系并非由PKC介导。
