Serotonin Increases Cilia-Driven Particle Transport via an Acetylcholine-Independent Pathway in the Mouse Trachea 英文参考文献.docVIP

SerotoninIncreasesCilia-DrivenParticleTransportviaan Acetylcholine-IndependentPathwayintheMouse Trachea PeterKo¨nig1.*,BenjaminKrain2.,GabrielaKrasteva2,WolfgangKummer2 1Institutfu¨rAnatomie,Zentrumfu¨rmedizinischeStruktur-undZellbiologie,Universita¨tzuLu¨beck,Lu¨beck,Germany,2Institutfu¨rAnatomieundZellbiologie,University ofGiessenLungCenter,Justus-Liebig-Universita¨t Giessen,Giessen,Germany Abstract Background: Mucociliary clearance in the airways is driven by the coordinated beating of ciliated cells. Classical neuromediators such as noradrenalin and acetylcholine increase ciliary beat frequency and thus cilia-driven transport. Despite the fact that the neuromediator serotonin is ciliostimulatory in invertebrates and has been implied in releasing acetylcholinefromtheairwayepithelium,itsroleinregulatingciliafunctioninvertebrateairwaysisnotestablished. Methodology/PrincipalFindings:Weexaminedtheeffectsofserotoninonciliarybeatfrequencyandcilia-drivenparticle transport in the acutely excised submerged mouse trachea and determined the sources of serotonin in this tissue by immunohistochemistry. Serotonin (100mM) increased cilary beat frequency (8.961.2Hz to 17.062.7Hz) and particle transportspeed(38.964.6mm/sto83.468.3mm/s)toanextentthatwascomparabletoasupramaximaldoseofATP.The increaseinparticletransportspeedwastotallypreventedbymethysergide(100mM).Blockadeofmuscarinicreceptorsby atropine (1mM) did not reduce the effect of serotonin, although it was effective in preventing the increase in particle transportspeedmediatedbymuscarine(100mM).Immunohistochemistrydemonstratedserotonininmastcellspointing towardsmastcellsandplateletsaspossibleendogenoussourcesofserotonin. Conclusions/Significance: These results indicate that serotonin is a likely endogenous mediator that can increase cilia- driventransportindependentfromacetylcholineduringactivationofmastcellsandplatelets. Citation:Ko¨nigP,KrainB,KrastevaG,KummerW(2009)SerotoninIncreasesCilia-DrivenParticleTransportviaan