Abstract

Formoterol (For) and salbutamol (Sal), two β2‐receptor agonistic drugs, are positively charged at physiological pH. Here, we investigated, if organic cation/carnitine transporters (OCT/Ns) are involved in the translocation of the drugs in human alveolar epithelial cells (A549). A549 cells were grown to confluent monolayers for 5 days. Investigation of OCT/N‐mediated transport was performed using [14C]‐tetraethylammonium (TEA, 10 μM), [3H]‐acetylcarnitine (5.5 nM, Ac‐Car) and the β2‐agonists (both at 500 μM) in KRB. A549 monolayers were incubated for 30 min (TEA) or 20 min (Ac‐Car) at 37°C. Competitive inhibition studies were also performed in which TEA uptake (0.25 – 2 mM) was studied in the presence and absence of For and Sal for 30 min. The β2‐agonists showed pronounced inhibition of TEA uptake into A549 monolayers. TEA uptake was decreased to 15.4% (For) and 54.5% (Sal) of control, respectively. Neither β2‐receptor agonist had a significant effect on Ac‐Car uptake. Eadie‐Hofstee analysis of TEA uptake revealed linearity and Km values of 858.2 μM and 1050.6 μM in the presence of For and Sal, respectively, which was a 6.5‐fold (For) and 4.5‐fold (Sal) increase compared to control values. No significant change in Vmax was observed. Ki values were 115 μM (For) and 271 μM (Sal). β2‐agonists competitively inhibited TEA uptake via OCTs, but no interaction between the drugs and OCTNs was found.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.