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Organic Cation Transport in Rabbit Alveolar Epithelial Cell Monolayers

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Abstract

Purpose. To characterize organic cation (OC) transport in primary cultured rabbit alveolar epithelial cell monolayers, using [l4C]-guanidine as a model substrate.

Methods. Type II alveolar epithelial cells from the rabbit lung were isolated by elastase digestion and cultured on permeable filters pre-coated with fibronectin and collagen. Uptake and transport studies of [14C]-guanidine were conducted in cell monolayers of 5 to 6 days in culture.

Results. The cultured alveolar epithelial cell monolayers exhibited the characteristics of a tight barrier. [14C]-Guanidine uptake was temperature dependent, saturable, and inhibited by OC compounds such as amiloride, cimetidine, clonidine, procainamide, propranolol, tetraethyl-ammonium, and verapamil. Apical guanidine uptake (Km = 129 ± 41 μM, Vmax = 718 ± 72 pmol/mg protein/5 min) was kinetically different from basolateral uptake (Km = 580 ± 125 (μM, Vmax = 1,600 ± 160 pmol/mg protein/5 min). [14C]-Guanidine transport across the alveolar epithelial cell monolayer in the apical to basolateral direction revealed a permeability coefficient (Papp) of (7.3 ± 0.4) × 10-7 cm/sec, about seven times higher than that for the paracellular marker [14C]-mannitol.

Conclusions. Our findings are consistent with the existence of carrier-mediated OC transport in cultured rabbit alveolar epithelial cells.

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Author notes

  1. Katharina J. Elbert

    Present address: Advanced Inhalation Research, Inc., Cambridge, Massachusetts, 02139

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Southern California, Los Angeles, California, 90033

    Jie Shen, Katharina J. Elbert & Vincent H. L. Lee

  2. Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany

    Claus-Michael Lehr

  3. Department of Drug Delivery Research, Kyoto University, Kyoto, Japan

    Fumiyoshi Yamashita

  4. Departments of Medicine, Physiology and Biophysics, Molecular Pharmacology and Toxicology, Biomedical Engineering, and, Will Rogers Institute Pulmonary Research Center, University of Southern California, Los Angeles, California, 90033

    Kwang-Jin Kim

  5. Department of Ophthalmology, University of Southern California, Los Angeles, California, 90033

    Vincent H. L. Lee

  6. Department of Pharmaceutical Sciences, PSC 704, University of Southern California, 1985 Zonal Avenue, Los Angeles, California, 90033

    Vincent H. L. Lee

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Shen, J., Elbert, K.J., Yamashita, F. et al. Organic Cation Transport in Rabbit Alveolar Epithelial Cell Monolayers. Pharm Res 16, 1280–1287 (1999). https://doi.org/10.1023/A:1014814017316

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