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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


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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


DOI: 10.1038/sj.bjp.0703518

PubMed id: 10960071


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