Ionic strength has a greater effect than does transmembrane electric potential difference on permeation of tryptamine and indoleacetic acid across Caco-2 cells.
The effects of transmembrane electric potential difference and ionic strength on the permeation of tryptamine and indoleacetic acid across a Caco-2 cell monolayer were examined. A decrease in the transmembrane electric potential difference caused by the addition of potassium ion to the transport buffer had no effect on the permeation rate of either compound. On the other hand, an increase in ionic strength resulted in a decrease in the permeation rate of tryptamine and an increase in the permeation rate of indoleacetic acid. The changes in the permeation rate with changes in the ionic strength were correlated with the membrane surface potential monitored by 1-anilino-8-naphthalenesulfonic acid (ANS), a fluorescent probe. We tested these effects using several other cationic and anionic compounds. These effects of ionic strength were found to be common to all drugs tested. The compound that showed a relatively lower permeation rate was given relatively stronger effect. The possibility of overestimation or underestimation caused by these effects should be considered when the permeation of an ionic compound is evaluated using a cell monolayer system.
Sugawara
Mitsuru
M
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
Kurosawa
Megumi
M
Sakai
Kasumi
K
Kobayashi
Michiya
M
Iseki
Ken
K
Miyazaki
Katsumi
K
D000817:Anilino Naphthalenesulfonates; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D004151:Dipeptides / Q000493:pharmacokinetics; D005456:Fluorescent Dyes; D006801:Humans; D007210:Indoleacetic Acids / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D014363:Tryptamines / Q000493:pharmacokinetics*
D000817:Anilino Naphthalenesulfonates; D004151:Dipeptides; D005456:Fluorescent Dyes; D007210:Indoleacetic Acids; D014363:Tryptamines; C004194:glycylsarcosine; C030820:tryptamine; C027132:1-anilino-8-naphthalenesulfonate; C030737:indoleacetic acid; D011188:Potassium