Adenosine stimulation of uphill adenine transport in L1210 leukemia cells. Evidence for a novel countertransport mechanism

R. L. Cybulski, D. W. Fry, I. David Goldman

Research output: Contribution to journalArticle

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Abstract

Adenine transport in the L1210 leukemia cell is mediated by a rapid facilitated process. Evidence supporting a carrier transport mechanism includes the observations that 1) extracellular hypoxanthine or xanthine inhibits net adenine uptake was 2) the presence of these bases within the intracellular compartment produces an uphill flow of adenine into the cell (countertransport). On the other hand, a very interesting phenomenon is observed when ATP-depleted cells are exposed simultaneously to extracellular adenosine and [3H]adenine in that there is a sustained uphill flow of [3H]adenine into the cell. A similar uphill flow of [3H]adenine into the cell results during simultaneous exposure of cells to inosine and [3H]adenine. Examination of the transport and metabolism of adenosine and its metabolites by high performance liquid chromatography demonstrates the basis for this phenomenon. Adenosine enters the cell by a mechanism distinct from that for adenine and is rapidly converted to inosine which can be further metabolized to hypoxanthine. Both of these compounds can flow out of the cell down their concentration gradients. The uphill flow of [3H]adenine into the cell is a result of a countertransport phenomenon with hypoxanthine in which hypoxanthine competes with intracellular [3H]adenine for efflux by the adenine carrier. Consistent with this hypothesis are the effects of deoxycoformycin and persantin. Persantin, an inhibitor of nucleoside transport, abolishes adenosine or inosine stimulation of adenine uptake by blocking the entry of these nucleosides into the cell. Deoxycoformycin, an inhibitor of adenosine deaminase, blocks only the adenosine stimulatory effect by preventing formation of inosine and consequently the subsequent conversion to hypoxanthine. As expected, deoxycoformycin does not alter the stimulatory effect of inosine on uphill transport of adenine.

Original languageEnglish (US)
Pages (from-to)4455-4459
Number of pages5
JournalJournal of Biological Chemistry
Volume256
Issue number9
StatePublished - 1981
Externally publishedYes

Fingerprint

Leukemia L1210
Active Biological Transport
Adenine
Adenosine
Inosine
Hypoxanthine
Pentostatin
Dipyridamole
Nucleosides
Adenosine Deaminase Inhibitors
Xanthine
Carrier transport
High performance liquid chromatography
Metabolites
Metabolism

ASJC Scopus subject areas

  • Biochemistry

Cite this

Adenosine stimulation of uphill adenine transport in L1210 leukemia cells. Evidence for a novel countertransport mechanism. / Cybulski, R. L.; Fry, D. W.; Goldman, I. David.

In: Journal of Biological Chemistry, Vol. 256, No. 9, 1981, p. 4455-4459.

Research output: Contribution to journalArticle

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