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Am J Physiol Lung Cell Mol Physiol 288: L93-L102, 2005. First published September 17, 2004; doi:10.1152/ajplung.00184.2004
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Adenovirus stimulates choline efflux by increasing expression of organic cation transporter-2

Olga L. Miakotina,1 Marianna Agassandian,1 Lei Shi,1 Dwight C. Look,1 and Rama K. Mallampalli1,2,3

Departments of 1Internal Medicine and 2Biochemistry; and 3Department of Veterans Affairs Medical Center, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa

Submitted 19 May 2004 ; accepted in final form 13 September 2004

We examined the effect of wild-type human adenovirus (Ad5) on choline transport in murine lung epithelia (MLE) and in rodent primary alveolar type II cells. Cells were active in pH-sensitive, reversible transport of choline, a process blocked pharmacologically with phenoxybenzamine, an inhibitor of organic cation transporters (OCT). PCR products for the choline transporters, OCT-1 and OCT-2, were detected, but only OCT-2 protein was robustly expressed within MLE and primary alveolar epithelial cells. Ad5 produced a two- to threefold increase in choline efflux from cells, resulting in a significant reduction in intracellular choline content and its major product, phosphatidylcholine. Effects of Ad5 on choline efflux were inhibited with phenoxybenzamine, and choline efflux was attenuated by OCT-2 small interfering RNA. Adenovirus also produced a dose-dependent increase in immunoreactive OCT-2 levels concomitant with increased cellular OCT-2 steady-state mRNA. These results indicate that adenoviruses can significantly disrupt choline trafficking in lung epithelia by upregulating expression of an alveolar protein involved in organic cation transport.

phenoxybenzamine; organic cation transporter


Address for reprint requests and other correspondence: R. K. Mallampalli, Pulmonary & Critical Care Div., C-33K, GH, Depts. of Internal Medicine & Biochemistry, Univ. of Iowa College of Medicine, Iowa City, IA 52242 (E-mail: rama-mallampalli{at}uiowa.edu)






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