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Inhibitory Potency of Marketed Drugs for Ulcerative Colitis and Crohn's Disease on PEPT1
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Otsuka Pharmaceut Co Ltd, Formulat Res Inst, BA Project, 224-18 Ebino,Kawauchi Cho, Tokushima 7710182, Japan..
Sekisui Med Co Ltd, ADME TOX Res Inst, 2117 Muramatsu, Ibaraki 3191182, Japan..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2017 (English)In: Biological and Pharmaceutical Bulletin, ISSN 0918-6158, E-ISSN 1347-5215, Vol. 40, no 9, p. 1572-1575Article in journal (Refereed) Published
Abstract [en]

We investigate the inhibitory effect of marketed drugs for treatment of inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) on the uptake transporters of peptide transporter 1 (PEPT1), which are up-regulated under the inflamed condition. The uptake transport of glycylsarcosine, a typical substrate for PEPT1, was reduced to 60% only by 5-aminosalicylate at the clinically relevant concentration among tested marketed drugs in PEPT1 transfected HEK293 cell lines. These findings suggest that the inhibition of PEPT1, which were up-regulated in inflamed or non-inflamed site on UC and CD patients, contribute to the clinical effect of commercially available drugs for IBD patients through the inhibition of uptake of antigenic proinflammatory oligopeptides such as formyl-methionine (Met)-leucine (Leu)-phenylalanine (Phe) via PEPT1.

Place, publisher, year, edition, pages
PHARMACEUTICAL SOC JAPAN , 2017. Vol. 40, no 9, p. 1572-1575
Keywords [en]
peptide transporter 1, 5-aminosalicylate, ulcerative colitis, Crohn's disease, intestinal absorption
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-335633ISI: 000409156600033PubMedID: 28867741OAI: oai:DiVA.org:uu-335633DiVA, id: diva2:1164936
Available from: 2017-12-12 Created: 2017-12-12 Last updated: 2018-01-13Bibliographically approved

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