Inhibition of Airway Constriction by Opioids Is Different down the Isolated Bovine Airway

Background: Opioid agonists attenuate in isolated airways contractile responses to electrical field stimulation (EFS), and this attenuation is mediated by opioid receptors. Differences exist in the density of muscarinic and β-adrenergic receptors between large and small airways. The authors hypothesized that the density of opioid receptors may also be different down the airway. Methods: The effects of three selective opioid agonists (μ, κ, δ) on EFS-induced contractions were compared between isolated bovine sublobar (4- or 5-mm inner diameter) and segmental (2- or 3-mm inner diameter) bronchial rings and between trachealis strips and bronchial rings. Results: D-Ala 2 -N-MePhe 4 -Gly-ol 5 enkephalin (DAMGO; 10 -5 M), a μ-opioid agonist, attenuated EFS-induced contractions of isolated sublobar and segmental bronchial rings at low stimulating frequencies of 0.5 Hz (P < 0.001), 2 Hz (P < 0.001), and 8 Hz (P < 0.001), but not at 32 Hz (P = 0.071). The inhibitory effect of DAMGO was antagonized by naloxone (10 -5 M) (P = 0.025). The selective κ-opioid agonist U-50488 H (10 -5 M) attenuated EFS-induced contractions at 32 Hz (P = 0.008) and 8 Hz (P = 0.045), but not at 2-Hz (P = 0.893) or 0.5-Hz (P = 0.145) contractions. The inhibitory effects of 10 -5 M U-50488 H were not antagonized by the highly selective κ-antagonist 2,2'-[1,1'-biphenyl] 4,4'-diyl-bis [2-hydroxy-4,4-dimethyl]-morpholinium (nor-BNI; 10 -5 M; P = 0.216) or naloxone (10 -5 M; P = 0.065). The selective δ-agonist D-penicillamine 2 -D-penicillamine 5 -enkephalin (DPDPE) (10 -5 M) had no inhibitory effects (P = 0.256). The inhibitory effects of the selective μ-opioid agonist DAMGO were smaller (P < 0.001) and those of U-50488 H larger (P < 0.001) in trachealis strips compared with bronchial rings. Conclusions: The attenuation of EFS-induced contractions by DAMGO in isolated bovine bronchi was mediated by prejunctional opioid receptors. In contrast, the inhibitory effect of U-50488 H was probably not mediated by opioid receptors in the bronchi.