Comparison of mucosal absorption-enhancing activity between a claudin-3/-4 binder and a broadly specific claudin binder.
Intercellular spaces between adjacent mucosal epithelial cells are sealed by tight junctions (TJs) that prevent the free movement of solutes across the epithelium. Claudins (CLs), a family of 27 integral membrane proteins, are essential components for TJ seals. We previously used a CL-3/-4 binder, the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), to show that CL modulation is a promising method to enhance mucosal absorption. Recently, by using a C-CPE mutant library, we developed a CL binder (m19) with broad specificity to CL-1, -2, -4, and -5. Here, we compared the mucosal absorption-enhancing activity of C-CPE and m19. Both CL binders enhanced jejunal absorption of dextran with a molecular mass of 4000 and 150,000 Da and nasal absorption of dextran with a mass of 4000 Da but not 150,000 Da in rats. Although both binders showed similar nasal absorption-enhancing activity of dextran (4000 Da), m19 exhibited a more potent jejunal absorption-enhancing effect than that of C-CPE. These findings suggest that mucosal absorption-enhancing activity may be modified by modulating CL specificity.
Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Koji
K
Matsuhisa
Masuo
M
Kondoh
Hidehiko
H
Suzuki
Kiyohito
K
Yagi
D000327:Adsorption; D000818:Animals; D002460:Cell Line; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism; D004768:Enterotoxins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D051379:Mice; D019108:Tight Junctions / Q000378:metabolism
D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; C568123:Cldn3 protein, mouse; C568124:Cldn3 protein, rat; C568158:Cldn4 protein, mouse; D003911:Dextrans; D004768:Enterotoxins; C035598:enterotoxin, Clostridium