Beta-2 Adrenergic Agonists Are Substrates and Inhibitors of Human Organic Cation Transporter 1

Molecular Pharmaceutics
Johanna J SalomonCarsten Ehrhardt

Abstract

Beta-2-adrenergic agonists are first line therapeutics in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Upon inhalation, bronchodilation is achieved after binding to β2-receptors, which are primarily localized on airway smooth muscle cells. Given that β2-adrenergic agonists chemically are bases, they carry net positive charge at physiologic pH value in the lungs (i.e., pH 7.4). Here, we studied whether β2-agonists interact with organic cation transporters (OCT) and whether this interaction exerted an influence on their passage across the respiratory epithelium to their target receptors. [14C]-TEA uptake into proximal (i.e., Calu-3) and distal (i.e., A549 and NCI-H441) lung epithelial cells was significantly reduced in the presence of salbutamol sulfate, formoterol fumarate, and salmeterol xinafoate in vitro. Expression of all five members of the OCT/N family has been confirmed in human pulmonary epithelial cells in situ and in vitro, which makes the identification of the transporter(s) responsible for the β2-agonist interaction challenging. Thus, additional experiments were carried out in HEK-293 cells transfected with hOCT1-3. The most pronounced inhibition of organic cation uptake by β2-agonists wa...Continue Reading

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Citations

Feb 3, 2016·Drug Metabolism and Pharmacokinetics·Yuma TegaKen-Ichi Hosoya
Jul 17, 2015·Journal of Pharmaceutical Sciences·Erica BäckströmMarkus Fridén
Aug 25, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Johanna J SalomonCarsten Ehrhardt
Feb 26, 2016·Expert Opinion on Drug Delivery·Sabrina NickelCarsten Ehrhardt
Oct 18, 2016·Journal of Pharmacological and Toxicological Methods·Malachy C UgwuRemigius U Agu
Aug 30, 2016·Molecular Pharmaceutics·Aateka PatelClive P Page
Sep 28, 2016·Journal of Pharmaceutical Sciences·Erica BäckströmMarkus Fridén
Dec 19, 2018·Frontiers in Pharmacology·Mitsuhiro Yamada, Masakazu Ichinose
Dec 20, 2019·Pharmacological Reviews·Hermann Koepsell
Aug 10, 2019·Pharmaceutics·Johanna J SalomonCarsten Ehrhardt
Dec 5, 2020·International Journal of Molecular Sciences·Mohammed Ali SeloJohanna J Salomon
Jan 9, 2021·Expert Opinion on Drug Delivery·Maria Gabriella MateraMario Cazzola
Nov 8, 2019·Biochemical Pharmacology·Kalyn M Rambacher, Nader H Moniri
Mar 9, 2021·Frontiers in Pharmacology·Shiwei ZhouYan Shu
Jul 14, 2021·Advanced Drug Delivery Reviews·Mohammed Ali SeloCarsten Ehrhardt

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