The effects of epithelial cell supernatant on contractions of isolated canine tracheal smooth muscle.
Airway epithelial cells produce mediators that play a role in regulating airway smooth muscle function. This study was designed to examine the effects of epithelial-derived products on contraction of airway smooth muscle. To avoid biochemical and physical changes that may be produced by stripping epithelium from tracheal smooth muscle, we examined the effect of products from pure cultured tracheal epithelial cells on intact dog tracheal smooth muscle. When bradykinin (10(-5) M) was added to dog epithelial cells in culture and the supernatant was added to strips of isolated tracheal smooth muscle, contractile responses to electrical field stimulation were significantly inhibited. Pretreatment of the epithelial cells with indomethacin (5.6 x 10(-6) M) inhibited this effect. Bradykinin placed directly on the canine smooth muscle had no effect on resting tension or on the response to electrical field stimulation. Contractions of the smooth muscle to exogenous acetylcholine were unaffected by supernatants from either indomethacin-treated or untreated cells stimulated with bradykinin (10(-5) M) compared to time controls. We conclude that bradykinin stimulates the release of a cyclooxygenase-dependent inhibitory factor from airway epithelial cells. This factor is likely to be prostaglandin E2, which is generated by the epithelial cells in response to bradykinin stimulation and inhibits smooth muscle contraction induced by electrical field stimulation. Although the mechanism of this inhibition is unknown, the normal response to exogenous acetylcholine is consistent with the hypothesis that prostaglandin E2 acts by inhibiting cholinergic neurotransmitter release at a prejunctional site.
Barnett
K
K
Cardiovascular Research Institute, University of California, San Francisco 94143.
Jacoby
D B
DB
Nadel
J A
JA
Lazarus
S C
SC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology*; D009994:Osmolar Concentration; D014132:Trachea / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D015232:Dinoprostone; D000109:Acetylcholine