title: Effects of capsaicin on intestinal cephalexin absorption in rats.
abstract: The effects of capsaicin on intestinal cephalexin absorption were investigated by means of in situ single pass perfusion in rats to clarify whether this pungent compound present in spice is a potential factor altering the intestinal drug absorption processes. Under the control condition, cephalexin was absorbed at a rate of 1.16+/-0.08 and 0.90+/-0.06 nmol/min/cm in the jejunum and ileum, respectively. The intestinal cephalexin absorption rate was decreased when capsaicin was dissolved in the perfusate at a concentration of 400 microM, being 0.54+/-0.07 and 0.46+/-0.10 nmol/min/cm in the jejunum and ileum, respectively. The inhibitive effect of capsaicin on intestinal cephalexin absorption was diminished when ruthenium red, a non-selective inhibitor of the transient receptor potential (TRP) cation channels, was intravenously infused into the rat during the experiment. Moreover, when we evaluated the paracellular permeability of cephalexin by utilizing a competitive inhibitor, glycylsarcosine, it was demonstrated that glycylsarcosine-insensitive intestinal cephalexin absorption in the jejunum was increased by 4.5 times in the presence of 400 microM capsaicin. These findings indicate that capsaicin affects both transcellular and paracellular pathways of intestinal cephalexin absorption by interacting with the TRP cation channels in intestinal tissues, in which capsaicin seems to change the transport activity of H+/peptide co-transporter 1 (PEPT1), and to a lesser degree, it seems to alter the paracellular permeability of the intestinal epithelia.
authors.affiliation: Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Komori
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Aiba
authors.forename: Risa
authors.initials: R
authors.lastname: Sugiyama
authors.forename: Chie
authors.initials: C
authors.lastname: Nakai
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kurosaki
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D002211:Capsaicin / Q000378:metabolism / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002506:Cephalexin / Q000493:pharmacokinetics*; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D000074011:Peptide Transporter 1; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D027981:Symporters / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D000900:Anti-Bacterial Agents; D004151:Dipeptides; D000074011:Peptide Transporter 1; D027981:Symporters; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D012430:Ruthenium Red; C004194:glycylsarcosine; D002506:Cephalexin; D002211:Capsaicin