Toggle Main Menu Toggle Search

Open Access padlockePrints

The Newcastle University research output collection, currently available on ePrints, will shortly be moving to a new open repository platform, Figshare. To prepare for the data migration we have paused adding new content to ePrints, and will resume once the new repository is launched. During this time you will continue to have access to ePrints (but no new content will appear). We will share updates here when available.

The organic cation transporter OCT2 mediates the uptake of β-adrenoceptor antagonists across the apical membrane of renal LLC-PK1 cell monolayers

Lookup NU author(s): Kelly Bleasby, Dr Colin Brown

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

1 Previous studies have shown that β-adrenoceptor antagonists may be substrates of organic cation transporters in kidney and lung. In this study we examined the transport of the β-adrenoreceptor antagonists propranolol and metoprolol, in renal LLC-PK1 cell monolayers. 2 Experiments with BCECF (2',7'-bis(2carboxyethyl)-5(6)-carboxyfluorescein) loaded LLC-PK1 cell monolayers demonstrated that metoprolol and propranolol flux across the basolateral membrane was consistent with non-ionic diffusion. Flux across the apical membrane consisted of both non-ionic diffusion and the uptake of the cationic form of the β-adrenoceptor antagonists. 3 Uptake of the cationic form of metoprolol across the apical membrane was Na+-independent, electrogenic and sensitive to external pH. Furthermore, uptake was sensitive to inhibition by Decynium-22 and the organic cations TEA (tetraethylammonium) and MPP+ (1-methyl 4-phenylpyridinium). These results, allied with the apical location of the uptake mechanism suggest that β-adrenoceptor antagonists may be substrates for the organic cation transporter, OCT2. 4 To confirm β-adrenoceptor antagonists as substrates for OCT2, we demonstrate, in cells transiently transfected with an epitope tagged version of hOCT2 (hOCT2-V5):(1) Decynium-22 sensitive [14C]-propranolol uptake, (2) cis-inhibition of OCT2 by a range of β-adrenoceptor antagonists and (3) metoprolol induced intracellular acidification.

Publication metadata

Author(s): Bleasby K; Brown CDA; Dudley AJ

Publication type: Article

Publication status: Published

Journal: British Journal of Pharmacology

Year: 2000

Volume: 131

Issue: 1

Pages: 71-79

ISSN (print): 0007-1188

ISSN (electronic): 1476-5381

Publisher: John Wiley & Sons

URL: http://dx.doi.org/10.1038/sj.bjp.0703518

DOI: 10.1038/sj.bjp.0703518

PubMed id: 10960071

Altmetrics

Altmetrics provided by Altmetric

Share