Absorption-enhancing mechanism of EDTA, caprate, and decanoylcarnitine in Caco-2 cells.
The mechanism of paracellular expansion by absorption enhancers, e.g., EDTA, sodium caprate (C10), and decanoylcarnitine (DC), was studied, the focus being on the process of actin microfilament contraction in the tight junction. The effects of various inhibitors such as KN-62 (a specific inhibitor of Ca2+/calmodulin dependent protein kinase), H7 (a protein kinase C (PKC) inhibitor), and W7 (a calmodulin antagonist) were examined on the paracellular expansion by the enhancers in Caco-2 cells. From the experimental results, the following mechanisms were suggested. EDTA activates PKC by depletion of extracellular calcium via chelation resulting in expansion of the paracellular route. C10 increases the intracellular calcium level by an interaction with the cell membrane independent of cell polarity resulting in contraction with actin microfilament. DC interacts specifically with the apical membrane to increase the intracellular calcium level, but the mechanistic details subsequent to the increase of calcium are not clear.
Tomita
M
M
Department of Biopharmaceutics, Tokyo University of Pharmacy and Life Science, Japan.
Hayashi
M
M
Awazu
S
S
D018938:Caco-2 Cells / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology*; D003911:Dextrans / Q000493:pharmacokinetics; D004533:Egtazic Acid / Q000494:pharmacology*; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism
D003652:Decanoic Acids; D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; C002893:decanoylcarnitine; C031071:decanoic acid; D004533:Egtazic Acid; D016650:Fluorescein-5-isothiocyanate; D002331:Carnitine; D002118:Calcium