title: Nicotine-morphine interactions at α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors.
abstract: 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 α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors. [(3)H]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 (86)Rb(+) efflux assays. Morphine displaced [(3)H]epibatidine from nicotinic agonist binding sites in all cell lines studied. The Ki values for morphine were 13.2μM in SH-EP1-hα4β2 cells, 0.16μM and 126μM in SH-SY5Y cells and 43.7μM in SH-EP1-hα7 cells. In SH-EP1-hα4β2 cells expressing α4β2 nicotinic acetylcholine receptors, morphine acted as a partial agonist of (86)Rb(+) efflux comparable to cytisine (with EC50 values of 53.3μM for morphine and 5.38μM 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 (86)Rb(+) ion efflux mediated by α3(⁎) nicotinic acetylcholine receptors. These results suggest that morphine acts as a partial agonist at α4β2 nicotinic acetylcholine receptors and as a weak antagonist at α3(⁎) nicotinic acetylcholine receptors.
authors: Division of Pharmacology and Toxicology, University of Helsinki, Finland. reeta.talka@helsinki.fi
authors: Reeta
authors: R
authors: Talka
authors: Outi
authors: O
authors: Salminen
authors: Paul
authors: P
authors: Whiteaker
authors: Ronald J
authors: RJ
authors: Lukas
authors: Raimo K
authors: RK
authors: Tuominen
mesh_terms: D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D004347:Drug Interactions; D006801:Humans; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D011725:Pyridines / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012414:Rubidium Radioisotopes / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium; D009020:Morphine; D009538:Nicotine; D011725:Pyridines; D011978:Receptors, Nicotinic; D012414:Rubidium Radioisotopes; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C403531:nicotinic receptor alpha4beta2; C082748:epibatidine