Effects of divalent cations, lanthanum, cation chelators and an ionophore on acetylcholine antinociception.
The antinociceptive effect of intracerebroventricularly administered acetylcholine as measured in the mouse tail-flick test was reduced by intracerebroventricularly injected calcium, magnesium and manganese. Maximum antagonism of acetylcholine-induced antinociception was observed with a 1-hour calcium pretreatment. Significant reduction existed at 2- but not 4-hour pretreatment. Barium and strontium were inactive. The antinociceptive effect of acetylcholine was potentiated by lanthanum and ethylene glycol tetraacetic acid but not by ethylenediamine tetraacetic acid. The ionophore A23187 was shown to increase greatly the antagonistic effect of a low dose of calcium. The ionophore alone did not significantly alter the effect of acetylcholine. Thus, it appears that calcium must penetrate cell membranes to reduce the effect of acetylcholine. In addition to acetylcholine, it was found that the antinociceptive effects of oxotremorine and physostigmine could also be reduced by calcium. These data indicate that alterations in intracellular calcium are involved in cholinergically induced antinociception.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004347:Drug Interactions; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010095:Oxotremorine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D010830:Physostigmine / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D002413:Cations, Divalent; D002614:Chelating Agents; D000001:Calcimycin; D010095:Oxotremorine; D007811:Lanthanum; D010830:Physostigmine; D002122:Calcium Chloride; D000109:Acetylcholine