The epithelial cholinergic system of the airways

Histochem Cell Biol. 2008 Aug;130(2):219-34. doi: 10.1007/s00418-008-0455-2. Epub 2008 Jun 20.


Acetylcholine (ACh), a classical transmitter of parasympathetic nerve fibres in the airways, is also synthesized by a large number of non-neuronal cells, including airway surface epithelial cells. Strongest expression of cholinergic traits is observed in neuroendocrine and brush cells but other epithelial cell types--ciliated, basal and secretory--are cholinergic as well. There is cell type-specific expression of the molecular pathways of ACh release, including both the vesicular storage and exocytotic release known from neurons, and transmembrane release from the cytosol via organic cation transporters. The subcellular distribution of the ACh release machineries suggests luminal release from ciliated and secretory cells, and basolateral release from neuroendocrine cells. The scenario as known so far strongly suggests a local auto-/paracrine role of epithelial ACh in regulating various aspects on the innate mucosal defence mechanisms, including mucociliary clearance, regulation of macrophage function and modulation of sensory nerve fibre activity. The proliferative effects of ACh gain importance in recently identified ACh receptor disorders conferring susceptibility to lung cancer. The cell type-specific molecular diversity of the epithelial ACh synthesis and release machinery implies that it is differently regulated than neuronal ACh release and can be specifically targeted by appropriate drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / biosynthesis
  • Acetylcholine / metabolism*
  • Animals
  • Choline O-Acetyltransferase / biosynthesis
  • Choline O-Acetyltransferase / genetics
  • Epithelial Cells / metabolism*
  • Epithelial Cells / ultrastructure
  • Humans
  • Neurons / metabolism
  • Organic Cation Transport Proteins / metabolism
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / ultrastructure
  • Symporters / metabolism*
  • Trachea / metabolism
  • Trachea / ultrastructure


  • Organic Cation Transport Proteins
  • Symporters
  • Choline O-Acetyltransferase
  • Acetylcholine