去酪氨酸1-D-苯丙氨酸3-β-酪蛋白吗啡跨越血脑屏障的体外渗透性

In vitro penetration of des-tyrosine1-D-phenylalanine3-beta-casomorphin across the blood-brain barrier.

作者信息

Stark H, Van Bree J B, de Boer A G, Jaehde U, Breimer D D

机构信息

Center for Bio-Pharmaceutical Sciences, State University of Leiden, The Netherlands.

出版信息

Peptides. 1992 Jan-Feb;13(1):47-51. doi: 10.1016/0196-9781(92)90138-s.

DOI:10.1016/0196-9781(92)90138-s

PMID:1620656

Abstract

The blood-brain barrier transport and metabolism of the synthetic beta-casomorphin (beta CM) derivative des-tyrosine1-D-phenylalanine3-beta-casomorphin (DT-D-Phe3-beta CM) were investigated using an in vitro model consisting of primary cultures of bovine cerebrovascular endothelial cells. DT-D-Phe3-beta CM was transported across the endothelial monolayer without significant metabolism. The endothelial permeability expressing the transport rate ranged between 1.4 and 2.2 cm x 10(-3)/min and was neither affected by luminal concentration changes (1 nM and 1 microM) nor different after luminal and abluminal administration. The metabolic inhibitor 2-desoxy-D-glucose did not affect the permeability of DT-D-Phe3-beta CM. These results suggest that DT-D-Phe3-beta CM is able to cross the blood-brain barrier by paracellular transport without using a carrier system.

摘要

利用由牛脑血管内皮细胞原代培养物组成的体外模型，研究了合成的β-酪蛋白吗啡（β-CM）衍生物去酪氨酸1-D-苯丙氨酸3-β-酪蛋白吗啡（DT-D-Phe3-β-CM）的血脑屏障转运和代谢。DT-D-Phe3-β-CM穿过内皮单层而无明显代谢。表示转运速率的内皮通透性在1.4至2.2 cm×10（-3）/min之间，既不受管腔浓度变化（1 nM和1 μM）的影响，在管腔给药和管腔外给药后也无差异。代谢抑制剂2-脱氧-D-葡萄糖不影响DT-D-Phe3-β-CM的通透性。这些结果表明，DT-D-Phe3-β-CM能够通过细胞旁转运穿过血脑屏障，而无需使用载体系统。