Morphine-evoked release of adenosine from the spinal cord occurs via a nucleoside carrier with differential sensitivity to dipyridamole and nitrobenzylthioinosine.
We have investigated the potential role of a bi-directional nucleoside carrier in the release of endogenous adenosine from spinal cord synaptosomes by examining the effects of dipyridamole and nitrobenzylthioinosine (NBI) on evoked release of adenosine. When 40 pmol adenosine were added to synaptosomes, only 70 +/- 2% was recovered, suggesting 30% uptake of adenosine. Dipyridamole (0.1-10 microM) reduced this uptake and also increased basal adenosine release, probably due to inhibition of the re-uptake of adenosine derived from released nucleotide. In contrast, NBI (0.1-10 microM) had no effect on either uptake of added adenosine or on basal release of adenosine. Addition of K+ (24 mM) and morphine (10 microM) produced a 50-60% increase in the release of adenosine, and this was reduced 35-98% by both dipyridamole and NBI (0.01-10 microM). Dipyridamole (0.01-1 microM) had no effect on the release of nucleotides (detected as adenosine) induced by noradrenaline, 5-hydroxytryptamine (5-HT) and capsaicin (50 microM each), although 10 microM dipyridamole significantly reduced release evoked by noradrenaline and 5-HT. This latter effect of dipyridamole was determined not to be due to inhibition of ATP release when measured directly. Within the spinal cord, there is a removal system for adenosine which is dipyridamole-sensitive but NBI-insensitive. Release of adenosine, but not nucleotides, appears to occur via this carrier system. The inhibition of release by NBI, but its lack of effect on uptake, suggests the involvement of heterogeneous carrier molecules in adenosine uptake and release from the spinal cord.
Sweeney
M I
MI
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
White
T D
TD
Sawynok
J
J
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D009705:Nucleosides / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D009705:Nucleosides; D012701:Serotonin; D013868:Thioinosine; D004176:Dipyridamole; D009020:Morphine; C001789:4-nitrobenzylthioinosine; D000241:Adenosine; D011188:Potassium; D002211:Capsaicin; D009638:Norepinephrine