Tropical and Infectious Research Centre, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz.
Daru. 2011;19(6):412-6.
Morphine-6-glucuronide (M6G) is a potent metabolite of morphine which has high penetration into the brain despite its high polarity, which could be the result of an active transport system involved in M6G transport through blood brain barrier. Examples of such transporters are p-glycoprotein (PGP), probenecid-sensitive transport mechanism, multidrug resistance related protein 1-3, the organic anion transporter family, and the organic anion transporter polypeptide family. The aim of present study was to elucidate the mechanisms involved in transporting morphine's potent metabolite, M6G.
M6G permeability via two cell lines; MDCKII and MDCK-PGP, was compared with that of sucrose. M6G transport was examined in different concentrations and in the presence of inhibitors of different transport systems such as cyclosporine, digoxin and probenecid. M6G concentration was measured using ELISA assay. The method was sensitive, reliable and reproducible.
The results confirmed that M6G could cross a layer of MDCK II or MDR-PGP cells more than sucrose could. It was also observed that M6G is a PGP transporter substrate. Its permeability was increased by the use of a PGP expressed cell line, and also in the presence of a strong PGP inhibitor. Digoxin related transporters such as Oatp2 may also involved in transport of M6G. M6G seemed to be a glucose transporter 1 substrate, but was not a substrate to probenecid sensitive transporters.
It is concluded that different transporters are responsible for M6G transports via different membrane, which could have effects on its pharmacokinetics or pharmacodynamics.
吗啡-6-葡萄糖醛酸苷（M6G）是吗啡的一种强效代谢物，尽管其极性很高，但仍能高度穿透血脑屏障进入大脑，这可能是一种参与 M6G 通过血脑屏障转运的主动转运系统的结果。这种转运体的例子有 p 糖蛋白（PGP）、丙磺舒敏感转运机制、多药耐药相关蛋白 1-3、有机阴离子转运体家族和有机阴离子转运多肽家族。本研究旨在阐明参与转运吗啡强效代谢物 M6G 的机制。
通过 MDCKII 和 MDCK-PGP 两种细胞系比较 M6G 的渗透性与蔗糖的渗透性。在不同浓度下，以及在不同转运系统抑制剂如环孢素、地高辛和丙磺舒存在的情况下，检查 M6G 的转运情况。使用 ELISA 测定 M6G 浓度。该方法灵敏、可靠且可重现。
结果证实，M6G 可以比蔗糖更穿过一层 MDCK II 或 MDR-PGP 细胞。还观察到 M6G 是 PGP 转运体的底物。使用表达 PGP 的细胞系可增加其通透性，并且在存在强 PGP 抑制剂时也可增加其通透性。Oatp2 等与地高辛相关的转运体也可能参与 M6G 的转运。M6G 似乎是葡萄糖转运蛋白 1 的底物，但不是丙磺舒敏感转运体的底物。
结论是不同的转运体负责通过不同的膜转运 M6G，这可能对其药代动力学或药效学产生影响。
