Morphine activates omega-conotoxin-sensitive Ca2+ channels to release adenosine from spinal cord synaptosomes.
Morphine-induced release of adenosine from the spinal cord is believed to contribute to spinal antinociception. Although this release is Ca2+ dependent, little is known of the nature of this dependence. In this study, the effects of the dihydropyridine L-type Ca2+ channel agonist Bay K 8644 and the antagonist nifedipine, the N-type Ca2+ channel antagonist omega-conotoxin, and ruthenium red, a blocker of Ca2+ influx induced by capsaicin, on release of adenosine evoked by morphine were determined. The effect of partial depolarization with a minimally effective concentration of K+ on morphine-evoked release of adenosine also was examined. Morphine 10(-5)-10(-4) M produced a dose-dependent enhancement of adenosine release from dorsal spinal cord synaptosomes. Following the addition of 6 mM K+ (total K+ concentration of 10.7 mM), 10(-6) M morphine also enhanced release, and an additional component of action at 10(-8) M was revealed. Release was Ca(2+)-dependent as it was not observed in the absence of Ca2+ and presence of EGTA. Bay K 8644 (10 nM) and nifedipine (100 nM) had no effect on the release of adenosine evoked by morphine, but omega-conotoxin (100 nM) markedly reduced such release in both the absence and the presence of the additional 6 mM K+. Morphine-evoked adenosine release was not altered in the presence of a partially effective dose of capsaicin, nor by ruthenium red.(ABSTRACT TRUNCATED AT 250 WORDS)
Cahill
C M
CM
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
White
T D
TD
Sawynok
J
J
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D020960:omega-Conotoxins
D015220:Calcium Channels; D004095:Dihydropyridines; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D012430:Ruthenium Red; D009020:Morphine; D000241:Adenosine