Methadone increases intracellular calcium in SH-SY5Y and SH-EP1-halpha7 cells by activating neuronal nicotinic acetylcholine receptors
| Autor: | Jian Hong Peng, Liisa Ahtee, Irene Kylänlahti, Jari Yli-Kauhaluoma, Ronald J. Lukas, Esa R. Korpi, Heli Nousiainen, Jukka S. Pakkanen, Raimo K. Tuominen, Tommi Möykkynen |
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| Rok vydání: | 2005 |
| Předmět: |
Agonist
medicine.medical_specialty Patch-Clamp Techniques Time Factors medicine.drug_class Pharmacology Receptors Nicotinic Ligands Biochemistry Binding Competitive 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Opioid receptor Internal medicine Cell Line Tumor Mecamylamine medicine Humans Fluorometry Nicotinic Agonists 030304 developmental biology Acetylcholine receptor Methyllycaconitine Neurons 0303 health sciences Chemistry Ryanodine receptor Intracellular Membranes 3. Good health Up-Regulation Analgesics Opioid Endocrinology Nicotinic agonist nervous system Epibatidine Calcium 030217 neurology & neurosurgery Methadone medicine.drug |
| Zdroj: | Journal of neurochemistry. 94(5) |
| ISSN: | 0022-3042 |
| Popis: | (-)-Methadone acts as an agonist at opioid receptors. Both (+)- and (-)-enantiomers of methadone have been suggested to be potent non-competitive antagonists of alpha3beta4 neuronal nicotinic acetylcholine receptors (nAChRs). In the present study, we have examined interactions of methadone with nAChRs by using receptor binding assays, patch-clamp recording and calcium fluorometry imaging with SH-SY5Y cells naturally expressing alpha7 and alpha3* nAChR subtypes and SH-EP1-halpha7 cells heterologously expressing human alpha7 nAChRs. Methadone potently inhibited binding of [3H]methyllycaconitine to alpha7 nAChRs and that of [3H]epibatidine to alpha3* nAChRs. Methadone pretreatment induced up-regulation of epibatidine binding sites in SH-SY5Y cells. Using whole-cell patch-clamp recording, both isomers of methadone activated cation currents via mecamylamine-sensitive nAChRs in SH-SY5Y cells. Nicotine and both (+)- and (-)-methadone evoked increases in [Ca2+]i in both fluo-3AM loaded cell lines, and these effects were blocked by mecamylamine and by the alpha7 selective antagonist methyllycaconitine, suggesting effects of methadone as alpha7-nAChR agonist. Sensitivity of sustained nicotine and methadone effects to blockade by CdCl2, ryanodine and xestospongin-c implicates voltage-operated Ca2+ channels and intracellular Ca2+ stores as downstream modulators of elevated [Ca2+]i. Collectively, our results suggest that methadone engages in complex and potentially pharmacologically significant interactions with nAChRs. |
| Databáze: | OpenAIRE |
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