Effect of pretreatment with bronchodilator drugs on in vitro responsiveness of guinea pig lung adenylate cyclase.

Pretreatment of guinea pigs with 5 microgram/kg isoprenaline or 10 microgram/kg salbutamol s.c. thrice daily for 7 days reduced the responsiveness of lung slice and tracheal ring adenylate cyclase to isoprenaline, but not to prostaglandin E1. Pretreatment of guinea pigs with isoprenaline also reduced the sensitivity of tracheal smooth muscle strip adenylate cyclase to isoprenaline. Cross-tolerance developed to noradrenaline in lung slices obtained from guinea pigs pretreated with isoprenaline. Propranolol blocked the response of lung slice adenylate cyclase of control and isoprenaline-pretreated animals to approximately the same degree. The presence of phentolamine in the incubation medium did not affect the reduced sensitivity to isoprenaline. Possible mechanisms of development of tolerance to sympathomimetic bronchodilator drugs are discussed.