ABSORPTION-ENHANCING MECHANISM OF SODIUM CAPRATE AND DECANOYLCARNITINE IN CACO-2 CELLS

Citation
M. Tomita et al., ABSORPTION-ENHANCING MECHANISM OF SODIUM CAPRATE AND DECANOYLCARNITINE IN CACO-2 CELLS, The Journal of pharmacology and experimental therapeutics, 272(2), 1995, pp. 739-743
Citations number
34
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00223565
Volume
272
Issue
2
Year of publication
1995
Pages
739 - 743
Database
ISI
SICI code
0022-3565(1995)272:2<739:AMOSCA>2.0.ZU;2-V
Abstract
The mechanism of action of the absorption enhancers such as sodium cap rate (C10) and decanoylcarnitine (DC) was examined. Both C10 and DC in creased the epithelial permeability of fluorescein isothiocyanate dext ran 4000 and decreased the transepithelial electrical resistance in Ca co-2 cell monolayer. irrespective of the presence or absence of mucosa l calcium, C10 rapidly increased intracellular calcium levels dose-dep endently. Compound 48/80, a phospholipase C inhibitor, prevented the i ncreases of the intracellular calcium level and permeability of fluore scein 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 sto res via activation of phospholipase C in plasma membrane. The increase of the calcium levels was considered to induce the contraction of cal modulin-dependent actin microfilament, followed by dilatation of the p aracellular route. Although DC also increased intracellular calcium le vels, neither compound 48/80 nor N-(6-aminohexyt)-5-chloro-1-naphthale nesulfonamide hydrochloride decreased the enhancing effect of DC. The enhancing mechanisms were different for C10 and DC.