Mechanism of the potentiation of neurally-induced bronchoconstriction by gallamine in the guinea-pig.
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.
Department of Pharmacology, Laboratori Guidotti S.p.A., Pisa, Italy.
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Del Monte
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Omini
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Subissi
D000109:Acetylcholine / Q000378:metabolism; D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D005703:Gallamine Triethiodide / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D002800:Cholinesterase Inhibitors; D010276:Parasympatholytics; D001285:Atropine; D002216:Captopril; D010830:Physostigmine; D011433:Propranolol; D011738:Pyrilamine; D000109:Acetylcholine; D005703:Gallamine Triethiodide