Nicotine-Morphine Interactions At Î±4Î²2 Î±7 And Î±3 Nicotinic Acetylcholine Receptors
Nicotine and opioids share several behavioral and rewarding properties. Although both opioids and nicotine have their own specific mechanism of action, there is empirical and experimental evidence of interactions between these drugs. We studied receptor-level interactions of nicotine and morphine at Î±4Î²2, Î±7 and Î±3 nicotinic acetylcholine receptors. [ 3H]epibatidine displacement was used to determine if morphine binds competitively to nicotinic acetylcholine receptors. Functional interactions of morphine and nicotine were studied with calcium fluorometry and 86Rb+ efflux assays. Morphine displaced [ 3H]epibatidine from nicotinic agonist binding sites in all cell lines studied. The Ki values for morphine were 13.2 Î¼M in SH-EP1-hÎ±4Î²2 cells, 0.16 Î¼M and 126 Î¼M in SH-SY5Y cells and 43.7 Î¼M in SH-EP1-hÎ±7 cells. In SH-EP1-hÎ±4Î²2 cells expressing Î±4Î²2 nicotinic acetylcholine receptors, morphine acted as a partial agonist of 86Rb+ efflux comparable to cytisine (with EC50 values of 53.3 Î¼M for morphine and 5.38 Î¼M for cytisine). The effect of morphine was attenuated concentration-dependently by the nicotinic antagonist mecamylamine. In the SH-SY5Y cell line expressing several subtypes of nicotinic acetylcholine receptors morphine had an inhibitory effect on nicotine induced 86Rb+ ion efflux mediated by Î±3 nicotinic acetylcholine receptors. These results suggest that morphine acts as a partial agonist at Î±4Î²2 nicotinic acetylcholine receptors and as a weak antagonist at Î±3 nicotinic acetylcholine receptors. Â© 2013 Elsevier B.V. All rights reserved.
European Journal of Pharmacology
Digital Object Identifier (DOI)
Talka, Reeta; Salminen, Outi; Whiteaker, Paul; Lukas, Ronald J.; and Tuominen, Raimo K., "Nicotine-Morphine Interactions At Î±4Î²2 Î±7 And Î±3 Nicotinic Acetylcholine Receptors" (2013). Translational Neuroscience. 392.