Serotonin Increases Cilia-Driven Particle Transport via an Acetylcholine-Independent Pathway in the Mouse Trachea

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 acetylcholine from the airway epithelium, its role in regulating cilia function in vertebrate airways is not established. Methodology/Principal Findings: We examined the effects of serotonin on ciliary beat frequency and cilia-driven particle transport in the acutely excised submerged mouse trachea and determined the sources of serotonin in this tissue by immunohistochemistry. Serotonin (100 mu M) increased cilary beat frequency (8.9+/-1.2 Hz to 17.0+/-2.7 Hz) and particle transport speed (38.9+/-4.6 mu m/s to 83.4+/-8.3 mu m/s) to an extent that was comparable to a supramaximal dose of ATP. The increase in particle transport speed was totally prevented by methysergide (100 mu M). Blockade of muscarinic receptors by atropine (1 mu M) did not reduce the effect of serotonin, although it was effective in preventing the increase in particle transport speed mediated by muscarine (100 mu M). Immunohistochemistry demonstrated serotonin in mast cells pointing towards mast cells and platelets as possible endogenous sources of serotonin. Conclusions/Significance: These results indicate that serotonin is a likely endogenous mediator that can increase cilia-driven transport independent from acetylcholine during activation of mast cells and platelets.