Spinal opioid receptors and adenosine release: neurochemical and behavioral characterization of opioid subtypes
Release of adenosine from the spinal cord contributes to spinal antinociception by morphine. Morphine induces a Ca(++)-dependent release of adenosine from dorsal spinal cord synaptosomes, which is augmented under partially depolarizing conditions. The present study examined the opioid receptor subty...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 275; no. 1; pp. 84 - 93 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.10.1995
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Subjects | |
Online Access | Get full text |
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Summary: | Release of adenosine from the spinal cord contributes to spinal antinociception by morphine. Morphine induces a Ca(++)-dependent
release of adenosine from dorsal spinal cord synaptosomes, which is augmented under partially depolarizing conditions. The
present study examined the opioid receptor subtypes involved in this release, and determined whether adenosine is an important
mediator of antinociception induced by the spinal administration of selective opioid agonists in rats. Nanomolar and micromolar
concentrations of the selective mu opioid agonists DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin) and PLO17 ([N-MePhe3,D-Pro4]morphiceptin)
induced release of adenosine in a biphasic manner in the presence of a partial depolarization (addition of 6 mM K+ to the
Krebs' medium). The delta opioid agonists DPDPE ([D-Pen2,D-Pen5]enkephalin) and DELT ([D-Ala2,Cys4]deltorphin) and the kappa
opioid agonist U50488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrroli-zemeacetamid e) had little effect on the release
of adenosine except at high micromolar concentrations. Release of adenosine by mu (nanomolar) and delta (micromolar) ligands
is Ca(++)-dependent, whereas the kappa (micromolar) receptor ligand releases adenosine via a Ca(++)-independent mechanism.
Behavioral antinociception using the hot-plate threshold test revealed that intrathecal administration of the mu and delta
opioid receptor agonists produced dose-dependent antinociception with an order of potency of DAMGO, PLO17 > morphine, DELT
> DPDPE. An ED75 dose of morphine, DAMGO or PLO17 was attenuated dose-dependently by intrathecal pretreatment with the adenosine
receptor antagonist caffeine. Caffeine did not block the antinociceptive response to delta agonists, but in fact augmented
antinociception when combined with DPDPE and DELT. This augmentation was dose-dependent. This study demonstrates that activation
of the mu receptor subtype is responsible for the opioid-induced release of adenosine from the spinal cord, that such release
contributes to the spinal antinociception by mu agonists and that only release evoked by low doses of opioids is behaviorally
relevant. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-3565 1521-0103 |