Premium
Morphine Activates ω‐Conotoxin‐Sensitive Ca 2+ Channels to Release Adenosine from Spinal Cord Synaptosomes
Author(s) -
Cahill C. M.,
White T. D.,
Sawynok J.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03234.x
Subject(s) - ruthenium red , adenosine , chemistry , morphine , synaptosome , agonist , pharmacology , depolarization , dihydropyridine , adenosine receptor , nifedipine , channel blocker , biophysics , calcium , receptor , biochemistry , medicine , biology , organic chemistry
Morphine‐induced release of adenosine from the spinal cord is believed to contribute to spinal antinociception. Although this release is Ca 2+ dependent, little is known of the nature of this dependence. In this study, the effects of the dihydropyridine L‐type Ca 2+ channel agonist Bay K 8644 and the antagonist nifedipine, the N‐type Ca 2+ channel antagonist ω‐conotoxin, and ruthenium red, a blocker of Ca 2+ 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 m M K + (total K + concentration of 10.7 m M ), 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 Ca 2+ and presence of EGTA. Bay K 8644 (10 n M ) and nifedipine (100 n M ) had no effect on the release of adenosine evoked by morphine, but ω‐conotoxin (100 n M ) markedly reduced such release in both the absence and the presence of the additional 6 m M K + . Morphine‐evoked adenosine release was not altered in the presence of a partially effective dose of capsaicin, nor by ruthenium red. These results indicate that morphine can stimulate two distinct phases of adenosine release from the spinal cord (nanomolar and micromolar), and that both phases of release are due to Ca 2+ entry via ω‐conotoxin‐sensitive N‐type Ca 2+ channels.