title: Functional nicotinic and muscarinic receptors on mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) are under the control of a large number of signaling systems. In this study, the presence and functionality of the acetylcholine (ACh) signaling system in MSCs was examined. We detected the expression of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and the presence of ACh in MSCs. MSCs also expressed the nicotinic acetylcholine receptor subunits alpha 3, alpha 5, alpha 7, and the muscarinic acetylcholine receptor 2 (M2-receptor). The M2-receptor and the nicotinic alpha 7 receptor subunits were expressed on distinct subpopulations of cells, indicating differential regulation of cholinergic signaling between MSCs. Stimulation of MSCs with the nicotinic receptor agonist nicotine and the muscarinic receptor agonist muscarine induced immediate and transient increases in intracellular Ca(2+) concentration. Furthermore, muscarine had an inhibiting effect on the production of the intracellular signaling molecule cyclic adenosine 3',5'-monophosphate (cAMP). The AChE inhibitor chlorpyrifos, which is widely used as an agricultural insecticide, had similar effects on intracellular Ca(2+) and cAMP in MSCs. Nicotine, muscarine, and chlorpyrifos induced the phosphorylation of extracellular signal-regulated kinases 1 and 2. This study demonstrates that several components of a cholinergic signaling system are present and functional in MSCs. Environmental compounds such as nicotine and agricultural insecticides can interfere with this system and may affect cellular processes in the MSC.
authors.affiliation: Department of Biology, University of York, York, North Yorkshire, United Kingdom. m.hoogduijn@erasmusmc.nl
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hoogduijn
authors.forename: Aixin
authors.initials: A
authors.lastname: Cheng
authors.forename: Paul G
authors.initials: PG
authors.lastname: Genever
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D021122:Protein Subunits; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D009538:Nicotine; D009116:Muscarine; D000242:Cyclic AMP; D002795:Choline O-Acetyltransferase; D048049:Extracellular Signal-Regulated MAP Kinases; D000110:Acetylcholinesterase; D004390:Chlorpyrifos; D002118:Calcium