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While the airway epithelium provides a diffusion barrier to the access of inhaled stimulants, it has recently been considered to have a more active physiological and pharmacological role in the regulation of the airway smooth muscle tone. The initial evidence for this comes from the fact that mechanical removal of the airway epithelium increases the in vitro responsiveness of airway smooth muscle to various spasmogens 3-5 times, although the nature of these regulatory mechanisms on the smooth muscle by the epithelium remains largely unresolved. One of the possible explanations is that the epithelium a generates factor(s) that inhibits the responsiveness of the underlying smooth muscle cells (epithelium-derived inhibitory or relaxing factor EpDIF/EpDRF). Furthermore, recent investigations revealed that airway epithelial cells also release a factor(s) that modulates the vascular smooth muscle tone, excitatory-neuroeffector transmission and resting membrane potential of the airway smooth muscle cells (epithelium-derived hyperpolarizing factor: EpDHF). This review will present and discuss the evidence indicating that the epithelium generates and releases a factor(s) that modulates smooth muscle tone, resting membrane potential of airway smooth muscle cells (EpDHF) and excitatory neuro-effector transmission in the airway.

Possible roles of airway epithelial cells in the control of airway smooth muscle tone.