Adenosine uptake site heterogeneity in the mammalian CNS? Uptake inhibitors as probes and potential neuropharmaceuticals.
Inhibitors of adenosine uptake or transport have been used clinically for some time in certain cardiovascular diseases. More recently, some of them have also been investigated for possible clinical use in combination with antimetabolites based on the observed heterogeneity of nucleoside transport in mammalian tumor cells. Such a heterogeneity of adenosine uptake and uptake sites has now also been suggested in the mammalian CNS. The aim of this article is, therefore, to review the present status of our knowledge of adenosine uptake in the mammalian CNS, compare it with our far more advanced knowledge of nucleoside transport in other mammalian cells and suggest direction of future research. The possible implications for the development of adenosine uptake inhibitors as adenosinergic neuropharmaceuticals will be discussed based on our knowledge of the physiological function of adenosine in the CNS.
Deckert
J
J
Universitats-Nervenklinik, Wurzburg, FRG.
Morgan
P F
PF
Marangos
P J
PJ
D000241:Adenosine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004176:Dipyridamole / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D009420:Nervous System / Q000187:drug effects; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D013868:Thioinosine; D004176:Dipyridamole; C001789:4-nitrobenzylthioinosine; D000241:Adenosine