Acetylcholine as a possible signaling molecule in embryonic stem cells: studies on survival, proliferation and death.
Acetylcholine (ACh) has always been regarded as a classical neurotransmitter that binds to nicotinic or muscarinic receptors and mediates signal transmission. The traditional view, that ACh acts solely as a neurotransmitter, has to be revised based on numerous findings demonstrating the existence of a non-neuronal cholinergic system. It is noteworthy that murine and human embryonic stem cells also synthesize ACh and express the enzyme acetylcholinesterase and muscarinic ACh receptors. Here, we investigated the possible role of ACh and AChRs in the regulation of embryonic stem cells. First, the expression of alpha3, alpha4, alpha7 and beta2 nicotinic receptor subunits in embryonic stem cells was investigated by RT-PCR. Second, in vitro studies have been conducted to assess the effects of ACh and its agonists on calcium dynamics, cell survival and proliferation. ACh and nicotine, but not muscarine could induce the mobilization of the intracellular Ca(2+). Interestingly, ACh increased the viability, but decreased the proliferation of embryonic stem cells. Our data provide evidence that ACh might exert its effect on stem cells by binding to specific receptors and modulating cell death and proliferation.
Landgraf
Dominic
D
Technische Universität Darmstadt, Developmental Biology and Neurogenetics, Schnittspahnstrasse 13, D-64287 Darmstadt, Germany.
Barth
Mareike
M
Layer
Paul G
PG
Sperling
Laura E
LE
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009116:Muscarine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011950:Receptors, Cholinergic; D009538:Nicotine; D009116:Muscarine; D000109:Acetylcholine