title: Effect of poly-L-arginine on intestinal absorption of hydrophilic macromolecules in rats.
abstract: We have already reported that poly-L-arginine (PLA) remarkably enhanced the in vivo nasal absorption of hydrophilic macromolecules without producing any significant epithelial damage in rats. In the present study, we examined whether PLA could enhance the absorption of a model hydrophilic macromolecule, fluorescein isothiocyanate-dextran (FD-4), across the intestinal mucosa, as well as the nasal mucosa, by an in situ closed-loop method using the rat intestine. PLA was found to enhance the intestinal absorption of FD-4 in a concentration-dependent manner within the concentrations investigated in this study, but segment-specific differences were found to be associated with this effect (ileum>jejunum>duodenum≧colon). The factors responsible for the segment-specific differences were also investigated by intestinal absorption studies using aprotinin, a trypsin inhibitor, and an analysis of the expression of occludin, a tight junction protein. In the small intestine, the differences in the effect of PLA on the absorption of FD-4 may be related to the enzymatic degradation of PLA. In the colon, the reduced effect of PLA on the absorption of FD-4 may be related to the smaller surface area for absorption and the higher expression of occludin compared with other segments.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan..
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yamaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Uchida
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kuwahara
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimazaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohtake
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Kimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.forename: Jun
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ogihara
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Hideshi
authors.initials: H
authors.lastname: Natsume
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010647:Phenyl Ethers / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007093:Imidazoles; C549414:N-3-trifluorophenoxy-3-phenylpropaneimidazole; D010455:Peptides; D010647:Phenyl Ethers; C015462:polyarginine