Airway opioid receptors mediate inhibition of cough and reflex bronchoconstriction in guinea pigs.
Effects of opioids and opioid antagonists on citric acid-induced cough and reflex bronchoconstriction have been examined in conscious guinea pigs. Airway reflexes produced by inhaled citric acid are mediated by capsaicin sensitive sensory neurons, and we examined particularly the possibility that inhibitory effects of opioids can be exerted locally in the airway. As expected, systemically administered codeine (1-10 mg/kg), meperidine (3-30 mg/kg) and morphine (1-10 mg/kg) dose-dependently inhibited cough and bronchoconstriction. However, inhalations of nebulized codeine (10-100 mg/ml) and morphine (10-30 mg/ml) also produced these effects. The potency and rapid onset of action of inhaled codeine suggest that it exerted its effects without first being metabolized to morphine. The opioid receptor antagonist naloxone completely (10-100 micrograms/kg), and nalorphine (a mixed agonist/antagonist) (1-3 mg/kg) partly, inhibited codeine's antitussive and antibronchoconstrictor effects. Nalorphine alone (3-30 mg/kg) inhibited citric acid induced reflexes, whereas naloxone was without effect. Prior inhalation of a quaternary opioid receptor antagonist, levallorphan methyl iodide (10 mg/ml), abolished the inhibitory effects of inhaled codeine (30 mg/ml). The present data suggest that inhibition of cough and reflex bronchoconstriction can be produced by opioids, acting on mu and kappa receptors located in the guinea pig tracheobronchial tree. The possible existence in the airways of a unique opioid receptor mediating inhibition of cough (as described in the central nervous system) cannot be excluded.
Karlsson
J A
JA
Pharmacological Laboratory, AB Draco, Lund, Sweden.
Lanner
A S
AS
Persson
C G
CG
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D003061:Codeine / Q000494:pharmacology; D003371:Cough / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008614:Meperidine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009269:Nalorphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000187:drug effects*
D002951:Citrates; D011957:Receptors, Opioid; D019343:Citric Acid; D009270:Naloxone; D009020:Morphine; D008614:Meperidine; D009269:Nalorphine; D003061:Codeine