Nonpurinergic nature and efficacy of nonadrenergic bronchodilation

The nonadrenergic inhibition of airway smooth muscle was investigated in vivo in the anesthetized cat. We examined 1) the bronchodilatating nature of the selective purinergic agonists [adenosine (AD) and adenosine triphosphate (ATP)], 2) antagonistic nature of aminophylline and quinidine, and 3) the comparative efficacy of nonadrenergic and sympathetic inhibition in reversing bronchoconstriction induced with serotonin. Alterations in smooth muscle tone were studied via electrical stimulation of the vagus nerves and measurements of pulmonary resistance. We found that neither AD nor ATP, aerosolized or injected, altered the tonic bronchoconstriction. Dipyridamole, an AD reuptake inhibitor, did not alter the response to AD, ATP, or electrical stimulation. Both aminophylline and quinidine block nonadrenergic dilatation at high dose levels (69 and 29 mg/kg, respectively); further, both reputed antagonists impair cholinergic excitation. Nonadrenergic inhibition is equipotent to sympathetic inhibition in reversing bronchoconstriction; however, nonadrenergic inhibition is more prolonged (4.0 +/- 1.8 min). We conclude that probably neither ATP nor AD is the neurotransmitter for nonadrenergic bronchodilatation in the cat, and that nonadrenergic inhibition is both potent and long lasting.