pH-dependent and carrier-mediated transport of salicylic acid across Caco-2 cells.
The transport of monocarboxylic acid drugs such as salicylic acid was examined in the human colon adenocarcinoma cell line, Caco-2 cells that possess intestinal epithelia-like properties. [14C]Salicylic acid transport was pH-dependent and appeared to follow the pH-partition hypothesis. However, 10 mM unlabelled salicylic acid significantly reduced the permeability coefficient of [14C]salicylic acid. Kinetic analysis of the concentration dependence of the permeation rate of salicylic acid across Caco-2 cells showed both saturable (Kt = 5.28 +/- 0.72 mM Jmax = 36.6 +/- 3.54 nmol min-1 (mg protein)-1) and nonsaturable (kd = 0.37 +/- 0.08 microL min-1 (mg protein)-1) processes. The permeation rate of [14C]salicylic acid was competitively inhibited by both acetic acid and benzoic acid, which were demonstrated in our previous studies to be transported in the carrier-mediated-transport mechanism which is responsible for monocarboxylic acids. Furthermore, certain monocarboxylic acids significantly inhibited [14C]salicylic acid transport, whereas salicylamide and dicarboxylic acids such as succinic acid did not. From these results, it was concluded that the transcellular transport of [14C]salicylic acid across Caco-2 cells is by the pH-dependent and carrier-mediated transport mechanism specific for monocarboxylic acids.
Takanaga
H
H
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Tamai
I
I
Tsuji
A
A
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000889:Anti-Arrhythmia Agents / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D001693:Biological Transport, Active / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects; D016014:Linear Models; D012459:Salicylates / Q000378:metabolism*; D020156:Salicylic Acid; D013696:Temperature; D014407:Tumor Cells, Cultured
D000085:Acetates; D000889:Anti-Arrhythmia Agents; D001565:Benzoates; D012459:Salicylates; D019817:Benzoic Acid; D020156:Salicylic Acid; D019342:Acetic Acid