Inhibition of cholinergic neurotransmission in human airways by opioids.
Opioids reduce the cholinergic responses to electrical field stimulation (EFS) in guinea pig and canine airways by a prejunctional effect. We determined whether a similar effect operates in human airways in vitro. [D-Ala2-NMePhe4-Gly-ol5]enkephalin (DAMGO) (10(-8)-10(-6) M), a selective mu-opioid receptor agonist, inhibited the response to EFS in a dose- and frequency-dependent manner. DAMGO (10(-6) M) produced 86% inhibition at 0.5 Hz and 38% inhibition at 4 Hz, but at 32 Hz there was no significant inhibition. Another selective mu-opioid receptor agonist H-Tyr-D-Arg-Gly-Phe(4-NO2)-Pro-NH2 diacetate (BW 443C) also inhibited responses to EFS, producing 57.7% inhibition at 4 Hz at a concentration of 10(-6) M. The inhibitory effect on EFS was blocked by the opioid receptor antagonist naloxone (10(-5) M), indicating that opioid receptors are involved. DAMGO (10(-6) M) had no effect on the contractile response to exogenous acetylcholine, indicating a prejunctional effect. We conclude that mu-opioid agonists inhibit cholinergic neurotransmission in human airways in vitro, and this could have therapeutic potential in the treatment of airway disease.
Belvisi
M G
MG
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Stretton
C D
CD
Verleden
G M
GM
Ledingham
S J
SJ
Yacoub
M H
MH
Barnes
P J
PJ
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C055303:BW 443C