The human and rat recombinant receptors for advanced glycation end products have a high degree of homology but different pharmacokinetic properties in rats

作     者：Renard, C Chappey, O Wautier, MP Nagashima, M Morser, J Scherrmann, JM Wautier, JL 

作者机构：Hop Lariboisiere Lab Rech Biol Vasc & Cellulaire EA 1557 F-75475 Paris France Hop Fernand Widal Inst Natl Sante & Rech Med U26 Paris France Berlex Biosci Richmond CA USA Inst Natl Transfus Sanguine F-75015 Paris France 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：1999年第290卷第3期

页      面：1458-1466页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

主　　题：白蛋白类/药代动力学 氨基酸序列 主动脉/代谢 毛细血管通透性/生理学 糖基化终产物 高级/代谢 分子序列数据 沉淀素试验 大鼠 Wistar 受体 免疫/遗传学 受体 免疫/代谢 序列同源性 氨基酸 组织分布 三氯乙酸/药理学 动物 牛 人类 男(雄)性 小鼠 大鼠 

摘      要：The accelerated formation of advanced glycation end products (AGEs) is implicated in diabetic microvascular and macrovascular complications. The binding of AGEs to their cellular surface receptor (RAGE) induces vascular dysfunction and in particular an increase in vascular permeability. We previously demonstrated that rat recombinant RAGE (rR-RAGE)produced in insect cells corrected the hyperpermeability due to RAGE AGE interaction and that pharmacokinetic properties of rR-RAGE after i.v. administration in rats were compatible with a potential therapeutic use. In the present study, we showed that recombinant human RAGE (rH-RAGE) had a similar efficacy in inhibiting AGE-induced endothelial, alteration and in reducing the hyperpermeability observed in streptozotocin-induced diabetic rats. I-125-rH-RAGE elimination half-life! after i.v. administration was similar in diabetic and normal rats (53.7 +/- 7.6 and 45.3 +/- 4.0 h, respectively). The presence of AGEs is responsible for a higher distribution volume in diabetic rats compared with normal rats (15.3 +/- 2.7 and 7.7 +/- 0.7 l/kg, respectively). Immunoreactive I-125-rH-RAGE decreased move rapidly than did immunoreactive I-125-rR-RAGE. The differences between I-125- rH-RAGE and I-125-rR-RAGE pharmacokinetics in rat may be related to differences in potential O-glycosylation and protease cleavage sites between the two RAGE molecules.