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Molecular Pharmacology, Vol 18, 40-44, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

A Common Basis for Inhibition of Nucleoside Transport by Dipyridamole and Nitrobenzylthioinosine?

ALAN R. P. PATERSON 1, EDA Y. LAU 1, EWA DAHLIG 1, and CAROL E. CASS 1

1 Cancer Research Unit (McEachern Laboratory) and Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

Transport of uridine by monolayer cultures of HeLa cells was inhibited by nitrobenzylthioinosine, dipyridamole, and lidoflazine. Biphasic concentration-effect curves were obtained for inhibition of nucleoside transport by nitrobenzylthioinosine, but not for inhibition by dipyridamole. Dipyridamole and lidoflazine interfered with high-affinity binding of [3H]nitrobenzylthioinosine to HeLa cells in an apparently competitive fashion; values of 1, 30, and 300 nM were obtained for dissociation constants, respectively, for nitrobenzylthioinosine, dipyridamole, and lidoflazine. The apparent competition with nitrobenzylthioinosine at the latter’s high-affinity binding sites suggests that dipyridamole and lidoflazine inhibit nucleoside transport by interaction with these sites.

Submitted on September 17, 1979
Accepted on January 21, 1980




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