title: Effects of acylcarnitines on efflux transporting system in Caco-2 cell monolayers.
abstract: This study examined the effects of the absorption enhancers, acylcarnitines, on efflux transporting systems, including P-glycoprotein (P-gp) and other efflux transporters, and elucidated the importance of acyl chain length and the concentration of acylcarnitine on the activity of efflux transport. The effects of two acyl (lauroyl and palmitoyl) carnitines on the influx and efflux of lucifer yellow and fluorescein isothiocyanate dextran 4,000, which have characteristic vectorial transport, were examined in Caco-2 cell monolayers. Lauroylcarnitine and palmitoylcarnitine increased influx and decreased efflux of these substrates, in a manner dependent on their concentration and acyl chain lengths by increasing influx and inhibiting efflux of the substrates. The results indicated that both the acyl moiety and long acyl chains play important roles in the modification of influx and efflux transport. Because no marked changes in the levels of P-gp protein or the leakage of LDH were observed at 1 h after the application of acylcarnitines, it was concluded that these acylcarnitines had an effect on modulation of the function of P-gp or other efflux transporters without cytotoxicity.
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. tomita@ps.toyaku.ac.jp
authors.forename: Mikio
authors.initials: M
authors.lastname: Tomita
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Doi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects*; D018938:Caco-2 Cells; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007848:Laurates / Q000494:pharmacology*; D010172:Palmitoylcarnitine / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003911:Dextrans; D005456:Fluorescent Dyes; D007546:Isoquinolines; D007848:Laurates; C015219:fluorescein isothiocyanate dextran; D010172:Palmitoylcarnitine; C091947:lauroylcarnitine; C017475:lucifer yellow; D007770:L-Lactate Dehydrogenase; D016650:Fluorescein-5-isothiocyanate; D002331:Carnitine