Kastin A J, Akerstrom V
VA Medical Center and Tulane University School of Medicine, New Orleans, LA 70112-1262, USA.
Peptides. 2001 May;22(5):829-34. doi: 10.1016/s0196-9781(01)00397-7.
Although urocortin is a potent inhibitor of food ingestion after peripheral administration, it was recently shown that under normal conditions this peptide crosses the blood-brain barrier (BBB) at a very slow rate. We examined whether hyperglycemia could stimulate the rate of entry (K(i)) of (125)I-urocortin into the mouse brain. In euglycemic mice, (125)I-urocortin injected iv entered the brain at a rate similar to that of the vascular marker (99m)Tc-albumin. However, injection of glucose (3 g/kg, ip) 0.5, 1, or 2 h before the (125)I-urocortin greatly increased the influx of urocortin. Without the glucose, the self-inhibition characteristic of a saturable transport system was not apparent. Self-inhibition could be demonstrated after the glucose injection, indicating activation of a transport system for urocortin that was saturable. Injection of insulin (10 U/kg, ip) 1 or 2 h before the (125)I-urocortin decreased the K(i). Thus, the entry of urocortin into brain can be activated by changes in the concentration of blood glucose, illustrating the responsiveness of the BBB to regulatory influences.
尽管尿皮质素在外周给药后是食物摄取的有效抑制剂，但最近有研究表明，在正常情况下，这种肽以非常缓慢的速度穿过血脑屏障（BBB）。我们研究了高血糖是否能刺激¹²⁵I - 尿皮质素进入小鼠脑内的速率（K(i)）。在血糖正常的小鼠中，静脉注射¹²⁵I - 尿皮质素进入脑内的速率与血管标志物⁹⁹ᵐTc - 白蛋白相似。然而，在注射¹²⁵I - 尿皮质素前0.5、1或2小时腹腔注射葡萄糖（3 g/kg），可显著增加尿皮质素的流入量。在未注射葡萄糖时，可饱和转运系统的自我抑制特性并不明显。注射葡萄糖后可证明存在自我抑制，这表明尿皮质素的可饱和转运系统被激活。在注射¹²⁵I - 尿皮质素前1或2小时腹腔注射胰岛素（10 U/kg）可降低K(i)。因此，血糖浓度的变化可激活尿皮质素进入脑内的过程，这说明了血脑屏障对调节影响的反应性。
