title: Electrical charge on protein regulates its absorption from the rat small intestine.
abstract: The effect of the electrical charge on the intestinal absorption of a protein was studied in normal adult rats. Chicken egg lysozyme (Lyz), a basic protein with a molecular weight of 14,300, was selected and several techniques for chemical modification were applied. Then the intestinal absorption of Lyz derivatives was evaluated by measuring the radioactivity in plasma and tissues, after the administration of an (111)In-labeled derivative to an in situ closed loop of the jejunum. After the administration of (111)In-Lyz, the level of radioactivity in plasma was comparable with the lytic activity of Lyz, supporting the fact that the radioactivity represents intact Lyz. (111)In-cationized Lyz showed a 2-3 times higher level of radioactivity in plasma, whereas the radioactivity of (111)In-anionized Lyz was much lower. The absorption rate of (111)In-Lyz derivatives calculated by a deconvolution method was correlated for the strength of their positive net charge. A similar relationship was observed using superoxide dismutase. These findings indicate that the intestinal absorption of a protein is, at least partially, determined by its electrical charge.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Makiya
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takakura
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D000838:Anions; D002412:Cations; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004563:Electrochemistry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D007205:Indium Radioisotopes; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D007700:Kinetics; D008297:Male; D018613:Microscopy, Confocal; D009113:Muramidase / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011506:Proteins / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000838:Anions; D002412:Cations; D005456:Fluorescent Dyes; D007205:Indium Radioisotopes; D011506:Proteins; D013482:Superoxide Dismutase; D009113:Muramidase; D016650:Fluorescein-5-isothiocyanate