title: Characterization of lipophilic drug binding to rat intestinal fatty acid binding protein.
abstract: Intestinal fatty acid binding protein (I-FABP) is present at high levels in the absorptive cells of the intestine (enterocytes) where it plays a role in the intracellular solubilization of fatty acids (FA). However, I-FABP has also been shown to bind to a range of non-FA ligands, including some lipophilic drug molecules, albeit with generally lower affinity than FA. The significance of these lower affinity interactions with exogenous compounds is not known. In this manuscript, we describe further characterization of drug-rat I-FABP binding interactions using a thermal-shift assay. A structural explanation of the observed affinity of rat I-FABP for different drugs based on spectroscopic data and modeling experiments is presented. In addition, immunocytochemistry has been used to probe the expression of I-FABP in a cell culture model reflective of the absorptive cells of the small intestine. Taken together, these data suggest a possible role for I-FABP in the disposition of some lipophilic drugs within the enterocyte.
authors.affiliation: Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, 3052, Victoria, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Velkov
authors.forename: Maria L R
authors.initials: ML
authors.lastname: Lim
authors.forename: James
authors.initials: J
authors.lastname: Horne
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Simpson
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Porter
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Scanlon
mesh_terms: D000818:Animals; D001665:Binding Sites; D018938:Caco-2 Cells; D020895:Enterocytes / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D018613:Microscopy, Confocal; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013696:Temperature
chemical_list: D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D008024:Ligands; D004364:Pharmaceutical Preparations; C006012:fenofibric acid; D011345:Fenofibrate