Modulation of free intracellular calcium and cAMP by morphine and cannabinoids, alone and in combination in mouse brain and spinal cord synaptosomes.
Changes in [Ca++]i and cAMP were evaluated as possible mechanisms by which the cannabinoids enhance the antinociception of morphine. The addition of subactive concentrations of delta 9-(THC) and morphine in combination to brain synaptosomes did not result in an enhanced decrease in [Ca++]i; however, this drug combination enhanced decreases in [Ca++]i in spinal cord synaptosomes. The combination of CP55,940 and morphine produced enhanced decreases in [Ca++]i in both brain and spinal cord synaptosomes. In brain synaptosomes, the combination of delta 9-THC and morphine produced an additive decrease in cAMP accumulation, whereas no significant change was observed with this combination in the spinal cord. Thus, the difference in the modulation of [Ca++]i but not cAMP in the brain in vitro may be a predictor of the greater-than-additive antinociceptive effects observe in vivo.
Pugh
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Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0613.
Welch
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Bass
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D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002186:Cannabinoids / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D003511:Cyclohexanols / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002186:Cannabinoids; D003511:Cyclohexanols; D009020:Morphine; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000242:Cyclic AMP; D002118:Calcium