Lin T H, Sugiyama Y, Sawada Y, Iga T, Hanano M
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Biochem Pharmacol. 1988 Aug 1;37(15):2957-61. doi: 10.1016/0006-2952(88)90281-x.
To elucidate the characteristics of promotion factor(s) in rat serum required for the protein-mediated transport of drugs into the brain, we examined the brain uptake of DL-propranolol as a model drug using the in vivo brain uptake index (BUI) method in rats. The protein-mediated transport was not observed in rats injected with the buffer solution containing either various concentrations of purified rat alpha 1-acid glycoprotein (alpha 1-AGP) or rat albumin. When the filtrate from rat serum was used as an injection vehicle to which a physiological concentration of purified rat serum protein(s) was added, the protein-mediated transport of DL-propranolol was observed in the rat brain. Moreover, the ability of protein-mediated transport of DL-propranolol was reduced in rats injected with the dialyzed serum compared with the undialyzed serum. These results suggest that the dialyzable promotion factor in serum is required for the protein-mediated transport of DL-propranolol into the brain.
为阐明蛋白质介导药物进入脑内所需的大鼠血清中促进因子的特性，我们采用体内脑摄取指数（BUI）法，以DL-普萘洛尔作为模型药物，研究了大鼠脑对其的摄取情况。在注射含有不同浓度纯化大鼠α1-酸性糖蛋白（α1-AGP）或大鼠白蛋白的缓冲溶液的大鼠中，未观察到蛋白质介导的转运。当将大鼠血清滤液用作注射载体并添加生理浓度的纯化大鼠血清蛋白时，在大鼠脑中观察到了DL-普萘洛尔的蛋白质介导转运。此外，与未透析血清相比，注射透析血清的大鼠中DL-普萘洛尔的蛋白质介导转运能力降低。这些结果表明，血清中可透析的促进因子是DL-普萘洛尔蛋白质介导进入脑内所必需的。
