Kawai N, McCarron R M, Spatz M
Stroke Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-4128, USA.
Neurosci Lett. 1995 May 5;190(2):85-8. doi: 10.1016/0304-3940(95)11507-s.
The effect of endothelins (ETs) on sodium/hydrogen (Na+/H+) antiport system was examined in cultured rat brain capillary endothelium (RBEC). ET-1, ET-2, and ET-3 stimulated Na+ uptake into RBEC with similar half-maximal stimulation (EC50) values (0.7, 0.6, and 1.1 nM, respectively). This reaction was inhibited by the Na+/H+ antiport inhibitor, N-(ethyl-N-isopropyl)-amiloride (EIPA). The selective endothelin A (ETA) receptor-antagonist (cyclo-D-Trp-D-Asp-Pro-D-Val-Leu (BQ123)), but not endothelin B (ETB) receptor-antagonists ((Cys11, Cys15)-ET-1 (IRL1038) or N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma MeLeu-D-Trp(COOMe)-D-Nle-ONa (BQ788)), inhibited both ET-1- and ET-3-stimulated Na+ uptake, indicating ETA-receptor mediation. The protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate (PMA)) failed to stimulate Na+ uptake. The calcium-calmodulin (CaM) inhibitor (W7) reduced ET-1-stimulated Na+ uptake by 50%, whereas the PKC inhibitor (staurosporine) had no effect, indicating that ET-1 stimulation of the Na+/H+ antiport system is linked to a CaM-dependent and PKC-independent pathway.
在内皮素（ETs）对培养的大鼠脑毛细血管内皮细胞（RBEC）钠/氢（Na+/H+）逆向转运系统的作用进行了研究。ET-1、ET-2和ET-3刺激RBEC摄取Na+，其半数最大刺激（EC50）值相似（分别为0.7、0.6和1.1 nM）。该反应被Na+/H+逆向转运抑制剂N-（乙基-N-异丙基）-阿米洛利（EIPA）抑制。选择性内皮素A（ETA）受体拮抗剂（环-D-色氨酸-D-天冬氨酸-脯氨酸-D-缬氨酸-亮氨酸（BQ123）），而非内皮素B（ETB）受体拮抗剂（（Cys11，Cys15）-ET-1（IRL1038）或N-顺式-2,6-二甲基哌啶羰基-L-γ-甲基亮氨酸-D-色氨酸（COOMe）-D-正亮氨酸-ONa（BQ788）），抑制ET-1和ET-3刺激的Na+摄取，表明是ETA受体介导。蛋白激酶C（PKC）激活剂（佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA））未能刺激Na+摄取。钙调蛋白（CaM）抑制剂（W7）使ET-1刺激的Na+摄取减少50%，而PKC抑制剂（星形孢菌素）无作用，表明ET-1对Na+/H+逆向转运系统的刺激与CaM依赖性和PKC非依赖性途径有关。
