Effects of K(+)-channel blockers on epithelium-derived relaxing factor (EpDRF)-mediated modulation of airway smooth muscle contractility.
Airway epithelium plays a role in the regulation of bronchial smooth muscle tone releasing cyclooxygenase products and epithelium-derived relaxing factor (EpDRF). To test possible involvement of K+ channels in the action of EpDRF, we studied rabbit tracheal segments in the presence of indomethacin under isometric conditions in vitro. Mechanical removal of the epithelium increased the contractile responses to acetylcholine, so that negative logarithm of the concentration required to produce 50% of maximal effect (pD2) 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-intact tissues, but the subsequent removal of the epithelium did not further potentiated the contractile responses. In contrast, apamin or glibenclamide had no effect on the epithelium-removal-induced potentiation of the contraction. The responses to electrical field stimulation were likewise potentiated by epithelial removal, an effect that was abolished by charybdotoxin. These results suggest that Ca(2+)-activated K+ channels are involved in the EpDRF modulation of airway smooth muscle responsiveness.
Tagaya
E
E
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tamaoki
J
J
Takeda
Y
Y
Takemura
H
H
Konno
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009569:Nitric Oxide; D000109:Acetylcholine