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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 4, pp 361–369 | Cite as

Carrier-mediated uptake of clonidine in cultured human lung cells

  • Marc Le Vée
  • Elodie Jouan
  • Olivier Fardel
Original Article
  • 147 Downloads

Abstract

The lung is a preferential organ site for accumulation of lipophilic basic amine drugs, so-called pneumophilic drugs and belonging to various pharmacological classes, which can result in lung toxicity. In order to investigate the mechanism involved in such pulmonary accumulation of drugs, uptake of clonidine, used here as a prototypical basic amine drug, was characterized in cultured human lung cells. Clonidine accumulation in lung alveolar A549 cells was found to be temperature- and pH-dependent; it was saturable, with a Michaelis–Menten affinity constant (Km) value of 569.4 μM. Various pneumophilic drugs, including amitriptyline, verapamil, propranolol, chlorpromazine, imipramine, and quinidine, markedly cis-inhibited clonidine uptake in A549 cells, in a dose-dependent manner for at least some of them. They additionally trans-stimulated clonidine efflux from A549 cells, thus suggesting that they are substrates for the putative clonidine transporter. In addition to alveolar A549 cells, bronchial epithelial BEAS-2B cells as well as lung endothelial HULEC-5a cells were found to exhibit clonidine accumulation abrogated by amitriptyline, verapamil, and chlorpromazine. Taken together, these data likely provided evidence for carrier-mediated uptake of clonidine in human lung cells. This carrier, which remains to be molecularly identified, interacts with various pneumophilic drugs, suggesting that it may contribute to lung accumulation of these drugs in a notable way.

Keywords

Clonidine Uptake Carrier Transport Lung Pneumophilic drugs 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

210_2018_1467_MOESM1_ESM.pdf (303 kb)
ESM 1 (PDF 302 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Université de Rennes 1RennesFrance
  2. 2.Pôle Biologie, Centre Hospitalier UniversitaireRennesFrance

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