E. Tagaya et al., EFFECTS OF K-CHANNEL BLOCKERS ON EPITHELIUM-DERIVED RELAXING FACTOR (EPDRF)-MEDIATED MODULATION OF AIRWAY SMOOTH-MUSCLE CONTRACTILITY(), Research communications in molecular pathology and pharmacology, 94(1), 1996, pp. 39-46
Airway epithelium plays a role in the regulation of bronchial smooth m
uscle tone releasing cyclooxygenase products and epithelium-derived re
laxing factor (EpDRF). To test possible involvement of K+ channels in
the action of EpDRF, we studied rabbit tracheal segments in the presen
ce of indomethacin under isometric conditions in vitro. Mechanical rem
oval of the epithelium increased the contractile responses to acetylch
oline, so that negative logarithm of the concentration required to pro
duce 50% of maximal effect (pD(2)) increased from 5.0 +/- 0.4 to 5.7 /- 0.3 (P < 0.01). Addition of charybdotoxin per se caused a leftward
shift of acetylcholine concentration-response curves in epithelium-int
act tissues, but the subsequent removal of the epithelium did not furt
her potentiated the contractile responses. In contrast, apamin or glib
enclamide had no effect on the epithelium-removal-induced potentiation
of the contraction. The responses to electrical field stimulation wer
e likewise potentiated by epithelial removal, an effect that was aboli
shed by charybdotoxin. These results suggest that Ca2+-activated K+ ch
annels are involved in the EpDRF modulation of airway smooth muscle re
sponsiveness.