Modulation of equine tracheal smooth muscle contractility by epithelial-derived and cyclooxygenase metabolites.
The role of epithelium in the modulation of contractile responses to electrical field stimulation (EFS), acetylcholine (ACh), and KCl were studied in vitro in strips of equine tracheal smooth muscle (TSM). EFS with 0.5 ms pulses of voltage (70 V) resulted in frequency dependent contractions of equine TSM that were sensitive to tetrodotoxin (TTX) and atropine. In TSM without epithelium, preincubation with indomethacin significantly potentiated contractile responses to EFS. The potentiating effect of indomethacin on EFS contractions was abolished by the addition of 3 nM prostaglandin E2 (PGE2). ACh and KCl cumulative concentration-response curves were shifted to the left by removal of epithelium from equine TSM strips with a significant decrease in the 50% effective concentration (EC50) for both ACh and KCl. The mean EC50 (+/- SE) for ACh in TSM without epithelium was 0.51 +/- 0.09 microM vs 4.30 +/- 1.03 microM in TSM with epithelium. Similarly, the mean EC50 (+/- SE) for KCl in TSM without epithelium was 22.20 +/- 2.61 mM vs 32.35 +/- 2.66 mM in TSM with epithelium. The addition of indomethacin (3 microM) had no effect on the ACh concentration-response curves in TSM strips with or without epithelium. Our results suggest that in the equine airway there is (1) an epithelial-derived relaxant factor that modulates tracheal smooth muscle contractility postsynaptically, and (2) a nonepithelial-derived inhibitory factor, possibly PGE2, that modulates ACh release from nerves presynaptically.
Tessier
G J
GJ
Department of Veterinary Biology, University of Minnesota, St Paul 55108.
Lackner
P A
PA
O'Grady
S M
SM
Kannan
M S
MS
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000494:pharmacology; D004558:Electric Stimulation; D006736:Horses; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
D001095:Arachidonic Acids; D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; C056250:epithelium-derived relaxant factor; D011189:Potassium Chloride; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000109:Acetylcholine; D007213:Indomethacin