Enhancement of the small intestinal uptake of phenylalanylglycine via a H+/oligopeptide transport system by chemical modification with fatty acids.
The transport characteristics of chemically modified phenylalanylglycine (Phe-Gly) with butyric acid (C4-Phe-Gly) and caproic acid (C6-Phe-Gly) were examined using rabbit intestinal brush-border membrane vesicles (BBMVs). In the presence of an inwardly H+ gradient (pH 7.5 inside, pH 6.0 outside), the uptake of Phe-Gly via BBMVs was significantly enhanced by the covalent attachment of butyric or caproic acid to the N-terminal of Phe-Gly. Moreover, C4-Phe-Gly uptake was stimulated by the trans-stimulation effect of some dipeptides and cefadroxil, and was inhibited by other dipeptides and cefadroxil. These results indicate that N-terminal modified Phe-Gly with fatty acids are transported into BBMVs via an oligopeptide transporter. Therefore, chemical modification of dipeptides with fatty acids can enhance the intestinal absorption of dipeptide by a carrier-mediated transport via an oligopeptide transporter.
Fujita
T
T
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Morishita
Y
Y
Ito
H
H
Kuribayashi
D
D
Yamamoto
A
A
Muranishi
S
S
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004151:Dipeptides / Q000493:pharmacokinetics*; D005227:Fatty Acids / Q000737:chemistry*; D007421:Intestine, Small / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism*; D011522:Protons; D011817:Rabbits
D002352:Carrier Proteins; D004151:Dipeptides; D005227:Fatty Acids; D009842:Oligopeptides; D011522:Protons; C040500:phenylalanylglycine