Effect of BW443C81, a novel opioid, on non-cholinergic bronchoconstrictor responses and neurogenic plasma extravasation in the guinea pig

Abstract

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.

Does nebulized fentanyl relieve dyspnea during exercise in healthy man?

“…These compensatory adaptations to tissue inflammation and damage are thought to facilitate the homeostatic regulation of peripheral inflammation by attenuating the excitability of peripheral sensory nerves to endogenous and perhaps also exogenous opioids (6,69). Indeed, in vitro studies have shown an inhibitory effect of mu-opioids on factors known to contribute to the pathophysiology and symptoms (e.g., dyspnea) of chronic inflammatory airway disease, including cholinergic neurotransmission and contraction of airway smooth muscle (7,11,55), neurogenic mucus hypersecretion (61), goblet cell secretion (35), and plasma extravasation (10,65). It is thus possible that the lack of benefit of nebulized fentanyl on exertional dyspnea in our study may be explained at least in part by inclusion of healthy younger men with no known or suspected history of chronic inflammatory airway disease.…”