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Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells.
J Pharmacol Exp Ther. 1998 Jan; 284(1):362-9.JP

Abstract

Medium chain fatty acids (MCFAs) are used to enhance the permeability of mucosal tissues to hydrophilic drugs, but their mechanism of action is largely unknown. In this study, the absorption-enhancing effects of the sodium salts of two MCFAs, capric acid (C10) and lauric acid (C12), were studied in monolayers of human intestinal epithelial Caco-2 cells. Both MCFAs induced a rapid increase in epithelial permeability to the hydrophilic marker molecule sodium fluorescein. Inhibition of phospholipase C and inhibition or activation of various kinases and buffering of intracellular calcium indicated that the effects on epithelial permeability were mediated through phospholipase C-dependent inositol triphosphate/diacylglycerol pathways. Surprisingly, the inositol triphosphate and diacylglycerol pathways were found to have opposing effects on paracellular permeability. Exposure to the MCFAs also resulted in a concentration dependent reduction of cellular dehydrogenase activity and ATP levels. C10, but not C12, induced redistribution of the tight junction proteins ZO-1 and occludin. These results indicate that the two MCFAs have partially different and more complex mechanisms than previously recognized, which has important implications for their use in vivo.

Authors+Show Affiliations

Department of Pharmacy, Uppsala University, Sweden.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9435199

Citation

Lindmark, T, et al. "Absorption Enhancement Through Intracellular Regulation of Tight Junction Permeability By Medium Chain Fatty Acids in Caco-2 Cells." The Journal of Pharmacology and Experimental Therapeutics, vol. 284, no. 1, 1998, pp. 362-9.
Lindmark T, Kimura Y, Artursson P. Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. J Pharmacol Exp Ther. 1998;284(1):362-9.
Lindmark, T., Kimura, Y., & Artursson, P. (1998). Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. The Journal of Pharmacology and Experimental Therapeutics, 284(1), 362-9.
Lindmark T, Kimura Y, Artursson P. Absorption Enhancement Through Intracellular Regulation of Tight Junction Permeability By Medium Chain Fatty Acids in Caco-2 Cells. J Pharmacol Exp Ther. 1998;284(1):362-9. PubMed PMID: 9435199.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. AU - Lindmark,T, AU - Kimura,Y, AU - Artursson,P, PY - 1998/1/22/pubmed PY - 1998/1/22/medline PY - 1998/1/22/entrez SP - 362 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 284 IS - 1 N2 - Medium chain fatty acids (MCFAs) are used to enhance the permeability of mucosal tissues to hydrophilic drugs, but their mechanism of action is largely unknown. In this study, the absorption-enhancing effects of the sodium salts of two MCFAs, capric acid (C10) and lauric acid (C12), were studied in monolayers of human intestinal epithelial Caco-2 cells. Both MCFAs induced a rapid increase in epithelial permeability to the hydrophilic marker molecule sodium fluorescein. Inhibition of phospholipase C and inhibition or activation of various kinases and buffering of intracellular calcium indicated that the effects on epithelial permeability were mediated through phospholipase C-dependent inositol triphosphate/diacylglycerol pathways. Surprisingly, the inositol triphosphate and diacylglycerol pathways were found to have opposing effects on paracellular permeability. Exposure to the MCFAs also resulted in a concentration dependent reduction of cellular dehydrogenase activity and ATP levels. C10, but not C12, induced redistribution of the tight junction proteins ZO-1 and occludin. These results indicate that the two MCFAs have partially different and more complex mechanisms than previously recognized, which has important implications for their use in vivo. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9435199/Absorption_enhancement_through_intracellular_regulation_of_tight_junction_permeability_by_medium_chain_fatty_acids_in_Caco_2_cells_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9435199 DB - PRIME DP - Unbound Medicine ER -