Nicotine-morphine interactions at α4β2, α7 and α3* 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 alpha 4 beta 2, alpha 7 and alpha 3* nicotinic acetylcholine receptors. [H-3]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 Rb-86(+) efflux assays. Morphine displaced [H-3]epibatidine from nicotinic agonist binding sites in all cell lines studied. The K-i values for morphine were 13.2 mu M in SH-EP1-h alpha 4 beta 2 cells, 0.16 mu M and 126 mu M in SH-SY5Y cells and 43.7 mu M in SH-EP1-h alpha 7 cells. In SH-EP1-h alpha 4 beta 2 cells expressing alpha 4 beta 2 nicotinic acetylcholine receptors, morphine acted as a partial agonist of Rb-86(+) efflux comparable to cytisine (with EC50 values of 53.3 mu M for morphine and 5.38 mu M 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 Rb-86(+) ion efflux mediated by alpha 3* nicotinic acetylcholine receptors. These results suggest that morphine acts as a partial agonist at alpha 4 beta 2 nicotinic acetylcholine receptors and as a weak antagonist at alpha 3* nicotinic acetylcholine receptors. (C) 2013 Elsevier B.V. All rights reserved.