Mechanism of the potentiation of neurally-induced bronchoconstriction by gallamine in the guinea-pig

Abstract

1. Electrical stimulation of the cervical vagi (15 Hz, 0.2 ms, 3 s, 7-15 V) produced a slight bronchoconstriction in the anaesthetized guinea-pig. This effect was fully abolished by atropine, while gallamine (0.1-10 mumol kg-1) produced a dose-dependent increase up to ten fold. 2. Gallamine-induced potentiation of neurally-mediated bronchoconstriction was not inhibited by depletion of sensory neuropeptides with capsaicin or by pretreatment with pyrilamine. In propranolol-pretreated guinea-pigs the potentiation induced by gallamine 3 and 10 mumol kg-1 was inhibited by 40 and 46%, respectively. 3. Physostigmine (0.5 mg kg-1) produced a very slight and slowly developing bronchoconstriction in the anaesthetized guinea-pig, which was also potentiated dose-dependently by gallamine (0.1-10 mumol kg-1). 4. Gallamine (10 mumol kg-1) potentiated the bronchial anaphylactic response induced by aerosol challenge with ovalbumin in actively sensitized guinea-pigs. 5. These results suggest that neither sensory neuropeptides nor histamine are involved in the gallamine-induced potentiation of neurally-mediated bronchoconstriction, while inhibition of the sympathetic nervous system may play a minor role. They are in general agreement with the hypothesis that gallamine antagonizes acetylcholine selectively at prejunctional muscarinic receptors in the guinea-pig airways, thus increasing its release from parasympathetic nerve terminals. These autoreceptors appear to be operant during anaphylactic bronchoconstriction.