MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by PATERSON, A. R. P.
Right arrow Articles by CASS, C. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by PATERSON, A. R. P.
Right arrow Articles by CASS, C. E.

Molecular Pharmacology, Vol 13, 1147-1158, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition by Nitrobenzylthioinosine of Adenosine Uptake by Asynchronous HeLa Cells

ALAN R. P. PATERSON 1, LORI R. BABB 1, JOHN H. PARAN 1, and CAROL E. CASS 1

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

Initial rates of adenosine uptake by HeLa cell monolayers were measured by a replicate culture technique. Under the assay conditions, the cellular content of adenosine was almost entirely in the form of metabolites, primarily ATP, ADP, and AMP, and thus the time course of adenosine uptake was essentially that of the formation of the adenosine phosphates; both time courses were linear and could be extrapolated through zero time. Adenosine uptake was mediated by a mechanism that appeared to be distinct from the thymidine, uridine, and guanosine uptake mechanisms. In the presence of nitrobenzylthioinosine (NBMPR), mediated entry of adenosine was eliminated and a nonsaturable component of uptake, evidently simple diffusion, was apparent. In the presence of partially inhibitory concentrations of NBMPR, the apparent Km values of the uptake process were increased and Vmax values were unchanged. In a structure-activity study, comparisons were made of inhibition of adenosine uptake by graded concentrations of various nucleoside derivatives related to NBMPR. Inhibitors more potent than NBMPR were identified, and it was apparent that the 2'-hydroxyl group of NBMPR and related compounds was not involved in the cell-inhibitor interaction. NBMPR and its 5'-monophosphate were comparable inhibitors of adenosine uptake.

Note:
ACKNOWLEDGMENTS We acknowledge with gratitude the generous provision of compounds for testing by the following: T. Fujii, J. P. Miller, R. A. Long, M. J. Robins, H. J. Schaeffer, L. R. Townsend, H. Vorbrüggen, and Developmental Therapeutics Program, National Cancer Institute, Bethesda, Md.

Submitted on February 1, 1977
Accepted on July 7, 1977




This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. K. Hinschen, R. B. Rose'Meyer, and J. P. Headrick
Age-related changes in A1-adenosine receptor-mediated bradycardia
Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H789 - H795.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics