Browse by author
Lookup NU author(s): Kelly Bleasby, Dr Colin Brown
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
1. In the kidney, a number of transport proteins involved in the secretion of permanently charged organic cations have recently been cloned. To evaluate the possible similarities between intestine and kidney in the handling of organic cations we investigated the transport of 1-methyl-4-phenylpyridinium (MPP+) across monolayers of intestinal Caco-2 cells. MPP+ is a prototypic substrate of the cloned organic cation transporters hOCT1 and hOCT2. 2. In Caco-2 cell monolayers, the basolateral to apical flux of MPP+ was significantly greater than the apical to basolateral flux, consistent with net secretion of MPP+. 3. Net secretion of MPP+ was abolished by addition of either 10 μM cyclosporin A or 100 μM verapamil to the apical membrane. In contrast, secretion of MPP+ was unaffected by addition of either TEA (2 mM) or decynium-22 (2 μM) to either apical or basolateral membranes. These results suggest that MPP+ secretion is mediated primarily by P-glycoprotein located at the apical membrane. We found no evidence of a role for hOCT1 or hOCT2 in the secretion of MPP+. 4. In addition to net secretion of MPP+, we found evidence of a Na+-dependent MPP+ uptake mechanism at the apical membrane of Caco-2 cells. 5. Na+-dependent MPP+ uptake was sensitive to inhibition by the organic cations; decynium-22 (2 μM), TEA (2 mM) and cimetidine (5 mM) but not by carnitine, guanidine or proline. 6. These results suggest that net secretion of MPP+ across the apical membrane of Caco-2 cells is a function of the relative contributions of MPP+ secretion mediated by P-glycoprotein and MPP+ absorption mediated by a novel Na+-dependent transport mechanism.
Author(s): Bleasby K, Chauhan S, Brown CDA
Publication type: Article
Publication status: Published
Journal: British Journal of Pharmacology
Year: 2000
Volume: 129
Issue: 3
Pages: 619-625
ISSN (print): 0007-1188
ISSN (electronic): 1476-5381
Publisher: John Wiley & Sons
URL: http://dx.doi.org/10.1038/sj.bjp.0703078
DOI: 10.1038/sj.bjp.0703078
PubMed id: 10711363
Altmetrics provided by Altmetric
