RT Journal Article
SR Electronic
T1 Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine in Caco-2 cells.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 739
OP 743
VO 272
IS 2
A1 M Tomita
A1 M Hayashi
A1 S Awazu
YR 1995
UL http://jpet.aspetjournals.org/content/272/2/739.abstract
AB The mechanism of action of the absorption enhancers such as sodium caprate (C10) and decanoylcarnitine (DC) was examined. Both C10 and DC increased the epithelial permeability of fluorescein isothiocyanate dextran 4000 and decreased the transepithelial electrical resistance in Caco-2 cell monolayer. Irrespective of the presence or absence of mucosal calcium, C10 rapidly increased intracellular calcium levels dose-dependently. Compound 48/80, a phospholipase C inhibitor, prevented the increases of the intracellular calcium level and permeability of fluorescein isothiocyanate dextran 4000 by C10. Furthermore, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride, a strong calmodulin inhibitor, also significantly decreased the enhancing effect of C10. These results suggest that C10 releases calcium from intracellular stores via activation of phospholipase C in plasma membrane. The increase of the calcium levels was considered to induce the contraction of calmodulin-dependent actin microfilament, followed by dilatation of the paracellular route. Although DC also increased intracellular calcium levels, neither compound 48/80 nor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride decreased the enhancing effect of DC. The enhancing mechanisms were different for C10 and DC.