Alteration in Ca2+ availability involved in antigen-induced airway hyperresponsiveness in rats.
The origin of Ca2+ contributing to the enhancement of acetylcholine-induced bronchial smooth muscle constriction in airway hyperresponsiveness induced by antigen challenge was investigated. Under Ca(2+)-free (concomitant with 10(-6) M nicardipine) conditions, the contractile responses of bronchial rings to 1 mM acetylcholine were significantly greater in rings from rats with hyperresponsive airways (0.15 +/- 0.04 g) than those of rings from normal rats (0.02 +/- 0.004 g; P < 0.05). The cumulatively administered Ca2+ induced a markedly greater bronchoconstriction in rings from rats with hyperresponsive airways in Ca(2+)-free solution when muscles were pretreated with 1 mM acetylcholine (in the presence of 10(-6) M nicardipine) than in rings from normal rats, whereas no significant difference in Ca(2+)-induced bronchoconstriction was observed between the two groups when muscles were pretreated with 60 mM K+ (in the presence of 10(-6) M atropine). These findings suggest that enhancement of the availability of Ca2+ released from intracellular stores and/or influxed through receptor-operated Ca2+ channels in airway smooth muscles might be involved in the airway hyperresponsiveness to acetylcholine in rats.
Chiba
Y
Y
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Misawa
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000633:toxicity; D017165:Ascaris suum / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000947:Antigens, Helminth; D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate; D009529:Nicardipine; D000109:Acetylcholine; D002118:Calcium