Rose J M, Audus K L
Department of Pharmaceutical Chemistry, The University of Kansas, School of Pharmacy, Lawrence 66047, USA.
J Cardiovasc Pharmacol. 1999 Jan;33(1):30-5. doi: 10.1097/00005344-199901000-00005.
The endothelial lining of the blood-brain barrier tightly controls the distribution of peptide hormones between the central nervous system and the circulation. By using primary cultures of brain microvessel endothelial cells, an in vitro model of the blood-brain barrier, we report here the uptake and transport of the octapeptide angiotensin II by a specific receptor population. With the angiotensin II antagonists losartan (AT1 specific) and PD 123,319 (AT2 specific), we showed that both the uptake and transport of angiotensin II were mediated by the AT1 receptor. Western blot analysis confirmed the existence of the AT1 receptor in our cell-culture model. Rhodamine 123 studies also suggested that both angiotensin II antagonists, but not angiotensin II, were substrates for the P-glycoprotein efflux system, thus restricting the transport of these compounds. These results suggest an AT1 receptor mediates uptake and transport of angiotensin II at the blood-brain barrier and may contribute to the regulation of cerebrovascular levels of the peptide.
血脑屏障的内皮细胞层严格控制着肽类激素在中枢神经系统和循环系统之间的分布。通过使用脑微血管内皮细胞的原代培养物（一种血脑屏障的体外模型），我们在此报告了八肽血管紧张素II通过特定受体群体的摄取和转运情况。使用血管紧张素II拮抗剂氯沙坦（特异性针对AT1）和PD 123,319（特异性针对AT2），我们发现血管紧张素II的摄取和转运均由AT1受体介导。蛋白质免疫印迹分析证实了我们细胞培养模型中存在AT1受体。罗丹明123研究还表明，这两种血管紧张素II拮抗剂而非血管紧张素II是P-糖蛋白外排系统的底物，从而限制了这些化合物的转运。这些结果表明，AT1受体介导血脑屏障处血管紧张素II的摄取和转运，可能有助于调节该肽在脑血管中的水平。
