Component of nicotine-induced intracellular calcium elevation mediated through α3- and α5-containing nicotinic acetylcholine receptors are regulated by cyclic AMP in SH-SY 5Y cells
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- Nirakar Sahoo
- editor
Description
<jats:p>The pathway from the medial habenular nucleus to the interpeduncular nucleus, in which nicotinic acetylcholine receptor (nAChR) including the α3 and α5 subunits (α3 * and α5 * nAChRs) are expressed, is implicated in nicotine dependence. We investigated whether α3 * and α5 * nAChRs are regulated by cAMP using SH-SY5Y cells to clarify the significance of these receptors in nicotine dependence. We analyzed the nicotine-induced elevation of intracellular Ca<jats:sup>2+</jats:sup> ([Ca<jats:sup>2+</jats:sup>]i). Nicotine induces a concentration-dependent increase in [Ca<jats:sup>2+</jats:sup>]i. The elimination of Ca<jats:sup>2+</jats:sup> from extracellular fluid or intracellular stores demonstrated that the nicotine-induced [Ca<jats:sup>2+</jats:sup>]i elevation was due to extracellular influx and intracellular mobilization. The effects of tubocurarine on nicotine-induced [Ca<jats:sup>2+</jats:sup>]i elevation and current suggest that intracellular mobilization is caused by plasma membrane-permeating nicotine. The inhibition of α3 *, α5 *, α7 nAChR and voltage-gated Ca<jats:sup>2+</jats:sup> channels by using siRNAs and selective antagonists revealed the involvement of these nAChR subunits and channels in nicotine-induced [Ca<jats:sup>2+</jats:sup>]i elevation. To distinguish and characterize the α3 * and α5 * nAChR-mediated Ca<jats:sup>2+</jats:sup> influx, we measured the [Ca<jats:sup>2+</jats:sup>]i elevation induced by nonmembrane-permeating acetylcholine when muscarinic receptors, α7nAChR and Ca<jats:sup>2+</jats:sup> channels were blocked. Under this condition, the [Ca<jats:sup>2+</jats:sup>]i elevation was significantly inhibited with a 48-h treatment of dibutyryl cAMP, which was accompanied by the downregulation of α3 and β4 mRNA. These findings suggest that α3 * and α5 * nAChR-mediated Ca<jats:sup>2+</jats:sup> influx is possibly regulated by cAMP at the transcriptional level.</jats:p>
Journal
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- PLOS ONE
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PLOS ONE 15 (11), e0242349-, 2020-11-30
Public Library of Science (PLoS)
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Keywords
Details 詳細情報について
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- CRID
- 1360009142795180160
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- ISSN
- 19326203
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- Data Source
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- Crossref
- KAKEN