title: Interaction of Peptide Transporter 1 With D-Glucose and L-Glutamic Acid; Possible Involvement of Taste Receptors.
abstract: We investigated the influence of sweet and umami (savory) tastants on the intestinal absorption of cephalexin (CEX), a substrate of peptide transporter 1 (PEPT1, SLC15A1) in rats. After oral administration of glucose or mannitol to rats, CEX was administered together with a second dose of glucose or mannitol. Western blot analysis indicated that expression of PEPT1 in rat jejunum membrane was decreased by glucose, compared to mannitol. Furthermore, the maximum plasma concentration (Cmax) of orally administered CEX was reduced by glucose compared to mannitol. The effect of glucose was diminished by nifedipine, a L-type Ca(2+) channel blocker. We also found that Cmax of orally administered CEX was reduced by treatment with L-glutamic acid, compared to D-glutamic acid. Thus, excessive intake of glucose and L-glutamic acid may impair oral absorption of PEPT1 substrates.
authors: Laboratory of Biopharmaceutics, Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.
authors: Hiroshi
authors: H
authors: Arakawa
authors: Laboratory of Biopharmaceutics, Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.
authors: Taichi
authors: T
authors: Ohmachi
authors: Laboratory of Biopharmaceutics, Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.
authors: Kiko
authors: K
authors: Ichiba
authors: Laboratory of Biopharmaceutics, Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.
authors: Hiroki
authors: H
authors: Kamioka
authors: Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, Takasaki, Japan.
authors: Takumi
authors: T
authors: Tomono
authors: Laboratory of Biopharmaceutics, Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.
authors: Masahiko
authors: M
authors: Kanagawa
authors: Laboratory of Biopharmaceutics, Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.
authors: Yoko
authors: Y
authors: Idota
authors: Laboratory of Biopharmaceutics, Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.
authors: Yasuko
authors: Y
authors: Hatano
authors: Laboratory of Biopharmaceutics, Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.
authors: Kentaro
authors: K
authors: Yano
authors: Department of Drug Absorption and Pharmacokinetics, Tohoku Pharmaceutical University, Sendai, Japan.
authors: Kaori
authors: K
authors: Morimoto
authors: Laboratory of Biopharmaceutics, Department of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan; Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, Takasaki, Japan. Electronic address: togihara@takasaki-u.ac.jp.
authors: Takuo
authors: T
authors: Ogihara
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002506:Cephalexin / Q000493:pharmacokinetics; D005947:Glucose / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D007408:Intestinal Absorption; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D000074011:Peptide Transporter 1; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects*; D027981:Symporters / Q000187:drug effects / Q000378:metabolism*; D013650:Taste Buds / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D000074011:Peptide Transporter 1; C489940:Slc15a1 protein, rat; D027981:Symporters; D018698:Glutamic Acid; D008353:Mannitol; D009543:Nifedipine; D005947:Glucose; D002506:Cephalexin
keywords: absorption; drug interactions; food effects; membrane translocation; peptide transporter