Effect of BW443C81, a novel opioid, on non-cholinergic bronchoconstrictor responses and neurogenic plasma extravasation in the guinea pig.
The novel, peripherally acting opioid peptide, BW443C81, which attenuates airway sensory nerve impulses, was examined on non-cholinergic (NC) constrictor responses in vitro and in vivo and neurogenic plasma extravasation in vivo in guinea-pig airways. Non-cholinergic contractions of guinea pig isolated bronchi, evoked by electrical field stimulation, were concentration-dependently inhibited by BW443C81 and morphine (10 nmol/1-100 mumol/l). In anaesthetised, artificially ventilated guinea pigs, frequency-related NC bronchoconstrictor responses evoked by antidromic electrical stimulation of the vagus nerves were reduced by BW443C81 (100 micrograms/kg/min i.v. infusion) and morphine (1 mg/kg i.v.). Neurogenic plasma extravasation produced by bilateral electrical vagal nerve stimulation in spontaneously breathing, anaesthetised guinea pigs was also inhibited by BW443C81 (1 mg/kg i.v.). The inhibitory effects of BW443C81 were reversed/prevented by naloxone. BW443C81 inhibits NC bronchoconstrictor responses and neurogenic plasma extravasation in guinea pig airways, consistent with its previously described mu-opioid receptor-mediated inhibitory action on airway sensory nerve function.
Shankley
C E
CE
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, UK.
Anderson
C W
CW
Adcock
J J
JJ
D000758:Anesthesia; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D012121:Respiration, Artificial
D000996:Antitussive Agents; D016085:Bronchoconstrictor Agents; D009842:Oligopeptides; D009270:Naloxone; D009020:Morphine; C055303:BW 443C