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.
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Acknowledgments
T. Velkov is the recipient of a Peter Doherty Fellowship (384300) from the National Health and Medical Research Council, Australia. This work was supported by grants from the Australian Research Council (DP0342458, DP0664069).
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Velkov, T., Lim, M.L.R., Horne, J. et al. Characterization of lipophilic drug binding to rat intestinal fatty acid binding protein. Mol Cell Biochem 326, 87–95 (2009). https://doi.org/10.1007/s11010-008-0009-x
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DOI: https://doi.org/10.1007/s11010-008-0009-x