Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells

Tuulikki Lindmark, Yukitaka Kimura, Per Artursson

Research output: Contribution to journalArticle

268 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)362-369
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume284
Issue number1
Publication statusPublished - Jan 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells'. Together they form a unique fingerprint.

  • Cite this