Naloxone-insensitive inhibition of acetylcholine release from parasympathetic nerves innervating guinea-pig trachea by the novel opioid, nociceptin.
The novel peptide, nociceptin and the mu-opioid agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) produced a concentration-dependent inhibition of electrical field stimulation (EFS)-evoked release of acetylcholine (ACh) from cholinergic nerves innervating guinea-pig trachea. The non-selective opioid receptor antagonist, naloxone, did not antagonize the inhibitory action of nociceptin under conditions where the inhibition of ACh release evoked by DAMGO was completely reversed. It is suggested that DAMGO and nociceptin can inhibit cholinergic, parasympathetic neurotransmission to the airways via the activation of classical (naloxone-sensitive) and novel (naloxone-insensitive) opioid receptors, respectively.
Patel
H J
HJ
Thoracic Medicine, Imperial College School of Medicine, National Heart & Lung Institute, London.
Giembycz
M A
MA
Spicuzza
L
L
Barnes
P J
PJ
Belvisi
M G
MG
D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists*; D014132:Trachea / Q000294:innervation* / Q000502:physiology; D000097629:Nociceptin
D000109:Acetylcholine; D009270:Naloxone; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin