title: Inhibition of airway constriction by opioids is different down the isolated bovine airway.
abstract: 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 beta-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 (mu, kappa, delta) 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-Ala2-N-MePhe4-Gly-ol5 enkephalin (DAMGO; 10(-5) M), a mu-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 kappa-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 kappa-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 delta-agonist D-penicillamine2-D-penicillamine5-enkephalin (DPDPE) (10(-5) M) had no inhibitory effects (P = 0.256). The inhibitory effects of the selective mu-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.
authors.affiliation: Servizio di Anestesia e Rianimazione, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Zappi
authors.forename: P
authors.initials: P
authors.lastname: Song
authors.forename: S
authors.initials: S
authors.lastname: Nicosia
authors.forename: F
authors.initials: F
authors.lastname: Nicosia
authors.forename: K
authors.initials: K
authors.lastname: Rehder
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000109:Acetylcholine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology*; D016084:Bronchoconstriction / Q000187:drug effects*; D002417:Cattle; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009294:Narcotics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists; D014132:Trachea / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000700:Analgesics; D004745:Enkephalins; D009294:Narcotics; D011759:Pyrrolidines; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D000109:Acetylcholine