Capsaicin-induced bronchoconstriction in the guinea-pig: contribution of vagal cholinergic reflexes, local axon reflexes and their modulation by BW443C81.
1 The objective of the study was to investigate the central vagal and local axon reflex components of bronchoconstrictor responses evoked by inhalation of capsaicin aerosol in anaesthetized guinea-pigs. This was accomplished by comparing the effects of bilateral vagotomy, atropine and the peripherally-acting polar enkephalin analogue, BW443C81, on bronchoconstrictor responses evoked by capsaicin. The effects of codeine were also determined. 2 Aerosols of capsaicin were generated from a 0.9 microgram ml-1 solution. Inhalation of capsaicin aerosol in 5, 10 and 15 breaths evoked dose-related bronchoconstrictor responses. The responses were immediate in onset and of extended duration. 3 Capsaicin-induced bronchoconstrictor responses were significantly inhibited following bilateral vagotomy or atropine (0.3 mg kg-1, i.v.) pretreatment by 46% +/- 14% (P less than 0.05) and 59% +/- 13% (P less than 0.01), respectively. 4 Administration of BW443C81 by intravenous infusion (3, 30 and 100 micrograms kg-1 min-1) caused a significant inhibition of capsaicin-induced bronchoconstrictor responses which achieved a greater maximum than either bilateral vagotomy or atropine. Codeine (100 micrograms kg-1 min-1, i.v.) did not significantly inhibit the bronchoconstrictor responses. 5 Inhibition of capsaicin-induced bronchoconstrictor responses by BW443C81 (30 micrograms kg-1 min-1, i.v.) was significantly (P less than 0.05) reduced by the peripherally-acting opioid antagonist N-methyl nalorphine (100 micrograms kg-1 min-1, i.v.). 6 These results show that capsaicin-induced bronchoconstrictor responses are mediated by at least two mechanisms, a vagal and/or cholinergic reflex pathway and a non-cholinergic pathway. BW443C81, but not codeine, significantly inhibited (P < 0.005) both mechanisms of capsaicin-induced bronchoconstriction probably by an action on peripheral opioid receptors located on vagal sensory nerves.
Buchan
P
P
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
Adcock
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001369:Axons / Q000187:drug effects*; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D003061:Codeine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D012018:Reflex / Q000502:physiology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D000996:Antitussive Agents; D009842:Oligopeptides; D001285:Atropine; C055303:BW 443C; D002211:Capsaicin; D003061:Codeine