inositol-1-4-5-trisphosphate and Bronchial-Hyperreactivity

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.

Topics: Acetylcholine; Animals; Antigens, Helminth; Ascaris suum; Bronchial Hyperreactivity; Bronchoconstriction; Calcium; Calcium Channels; Disease Models, Animal; Dose-Response Relationship, Drug; Inositol 1,4,5-Trisphosphate; Male; Muscle Contraction; Muscle, Smooth; Nicardipine; Rats; Rats, Wistar