Agonist-induced contractile responses of human bronchial muscle in vitro: effects of Ca2+ removal, La3+ and PY108068.

The effects of reducing the extracellular Ca2+ concentration ([Ca2+]0), the effects of La3+ and the dihydropyridine Ca2+ entry blocker PY108068 on contractile responses in human isolated bronchial strips have been compared. Reducing [Ca2+]0 or the presence of La3+ (1 mM) caused a reduction in basal tone, whereas PY108068 (1 microM) had no effect on unstimulated preparations. Response to KCl and A23187 were, in general, more markedly depressed by reducing the entry of extracellular Ca2+, with La3+ or PY108068 than were those to histamine, methacholine and LTD4. The effects of reducing [Ca2+]0, La3+ and PY108068 on responses to the receptor-mediated agents suggest that intracellular Ca2+ may be mobilized upon receptor activation, whereas responses to KCl and A23187 appear to be dependent upon the influx of extracellular Ca2+. More than one source of activator Ca2+ can therefore be involved in the development of contractions in human airway smooth muscle. These findings are in accord with those observed for in vitro airways preparations from experimental animals.