[3H]Adenosine transport in DDT1 MF-2 smooth muscle cells: Inhibition by metabolites of propentofylline

Fiona E. Parkinson, Kallol Mukherjee, Jonathan D. Geiger

Research output: Contribution to journalArticle

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Abstract

Adenosine receptor signal transduction mechanisms have previously been characterized in Syrian hamster smooth muscle DDT1 MF-2 cells but adenosine transport in these cells has not. DDT1 MF-2 cells possess a high density (370,000 sites/cell) of high affinity (K(d) value of 0.26 nM) binding sites for [3H]nitrobenzylthioinosine, a marker for the equilibrative and inhibitor-sensitive subtype of nucleoside transporters. Transport of [3H]adenosine was insensitive to Na+ and was inhibited by the nucleoside transport inhibitors nitrobenzylthioinosine, dilazep and dipyridamole with IC50 values of 1, 13 and 270 nM, respectively. Propentofylline, a neuroprotective compound that can inhibit nucleoside transporters, is rapidly metabolized in vivo to the racemate (±)-A720287. Based on recent findings that some transport inhibitors exhibit marked stereoselectivity, we tested the degree to which individual stereoisomers of (±)-A720287 affect adenosine transport. Propentofylline inhibited [3H]adenosine transport in DDT1 MF-2 cells with an IC50 value of 24 μM. (±)-A720287 and the individual stereoisomers (+)-833791 and (-)-844261 had similar potency to propentofylline for inhibition of [3H]adenosine transport in DDT1 MF-2 cells as well as in clonal mouse leukemia L1210/B23.1 cells, cells which possess only the equilibrative and inhibitor-sensitive subtype of nucleoside transporters. Thus, the neuroprotective effects of propentofylline may be due, in part, to the primary metabolites of propentofylline.

Original languageEnglish (US)
Pages (from-to)97-102
Number of pages6
JournalEuropean Journal of Pharmacology
Volume308
Issue number1
DOIs
Publication statusPublished - Jul 11 1996

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Keywords

  • Adenosine
  • Nitrobenzylthioinosine
  • Nucleoside transport
  • Propentofylline

ASJC Scopus subject areas

  • Pharmacology

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