Differential effects of divalent cations, cation chelators and an ionophore (A23187) on morphine and dibutyryl guanosine 3': 5'-cyclic monophosphate antinociception.
The effects of intraventricularly (i.c.v.) administered divalent cations, cation chelators and an ionophore (A23187) on antinociception produced by i.c.v. administration of morphine or dibutyryl guanosine 3':5'-cyclic monophosphate (db c-GMP) were quantitated in the mouse tail-flick procedure. Ca++ pretreatment produced a dose-related potentiation (> 10-fold) of db c-GMP and a dose-related antagonism (> 20-fold) of morphine antinociception. Mg++ pretreatment antagonized db c-GMP, whereas morphine antinociception was unaffected. Ba++ and Sr++ were observed to possess intrinsic antinociceptive activity. Administration of Ba++ or Sr++ had greater than additive effects on db c-GMP and morphine antinociception. EDTA pretreatment did not affect db c-GMP or morphine antinociception. Ethylene glycol bis(beta-aminoethyl ether)N,N-tetraacetic acid had no effect on db c-GMP but potentiated the morphine response. The ionophore A23187 had no effect on db c-GMP or morphine in the tail-flick test. However, A23187 potentiated the effect of high doses of Ca++ on db c-GMP and increased the antagonistic effect of a low dose of Ca++ on morphine antinociception. The results provide further evidence that the mechanism of db c-GMP antinociception is different from that of morphine.
D000700:Analgesics; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002413:Cations, Divalent / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*
D000700:Analgesics; D002413:Cations, Divalent; D002614:Chelating Agents; D003995:Dibutyryl Cyclic GMP; D000001:Calcimycin; D009020:Morphine; D006152:Cyclic GMP; D002118:Calcium