Acetylcholine inhibits cell cycle progression in rat Schwann cells by activation of the M2 receptor subtype

Cultures of schwalla cells froill ncoaatal rat sciatic aenes ivere treated with acety1cholilic agonists tvid the cjj cts oil cell Prolificratiou cniluatcd. 3[HI-thyaiidiac incorporation shows that accty1choliac (ACh) receptor agoiiists ilillibit cell proliftratioti, aiid FACS analysis deinoustratcs ccll-cyclc arrest and accunlulatioii of cells ill the Gi phase. The use of arecaiditie, a selective agouist of niuscariiiic M2 receptors reveals that this effect depends nictitily oil jW2 receptor acth,atioii. The arecaidine i1cpetialci i t- block ill Gi is rci,ersible becausc reinoval of arecaidiue froai the culture iiieditaii mduccs progrcssioil to the S phase. The block of the Gj-S transitioil is also characterized by inodulatiou of the expressioti ofscwrol cell-cycic inarkcrs. Morcoi,cr, trcatnicat ivith ACh receptor agmist causes both a decreasc ill the PCNA prolcin lci,cls ill Schivaiiii cell iniclci aad all iiicreasc ill P27 Olld P53 proteins. Filially, iinnnuio-elcctrou inicroscopy dcalonStl-atCS that M2 receptors arc expressed by Schivanii cells ill i,ivo. These results inclicate that ACh, by aiodulatiiig Schwaiin cell prolificratioii through M2 I-CCCPtOl- aclivatioa,)iiight cowributc to their progression to a niore dif rewiated phenotype.