Role of Ca(2+)-activated K+ channel in epithelium-dependent relaxation of human bronchial smooth muscle.
1. To elucidate whether K+ channels play a role in the action of epithelium-dependent bronchodilatation, we studied responses in human bronchial strips in the presence of indomethacin and NG-nitro-L-arginine methylester under isometric conditions, in vitro. 2. Mechanical removal of the epithelium increased the contractile responses to acetylcholine; the pD2 values increased from 5.0 +/- 0.2 to 5.9 +/- 0.3 (P < 0.001). This potentiation was abolished by iberiotoxin but not by apamin or glibenclamide. 3. In cascade bioassay, application of the bathing medium from dispersed, bronchial epithelial cells to epithelium-denuded bronchial strips decreased acetylcholine-induced contraction by 44 +/- 6%. This effect was reduced to 10 +/- 3% (P < 0.01) when the epithelial cells were pretreated with iberiotoxin, and to 4 +/- 1% (P < 0.001) when the epithelial cells were incubated with Ca(2+)-free medium containing [1,2-bis(2) aminophenoxy] ethane N,N,N',N'-tetraacetic acid-acetomethoxy ester. 4. In contrast, the bronchodilator effect of the medium bathing epithelial cells was not altered by the direct addition of iberiotoxin to epithelium-denuded tissues. 5. These results suggest that the Ca(2+)-activated K+ channel may play a role in the synthesis and/or release of smooth muscle relaxing factor, which is neither nitric oxide nor a cyclo-oxygenase product, from airway epithelial cells.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tagaya
E
E
Isono
K
K
Kondo
M
M
Konno
K
K
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001030:Apamin / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology
D007004:Hypoglycemic Agents; D010455:Peptides; D015221:Potassium Channels; D001030:Apamin; D009569:Nitric Oxide; C064719:iberiotoxin; D000109:Acetylcholine; D005905:Glyburide; D002118:Calcium