The antitussive effects of endomorphin-1 and endomorphin-2 in mice.
The antitussive effects of endomorphin-1 and endomorphin-2, endogenous mu-opioid receptor agonists, on capsaicin-induced coughs were examined in mice. Endomorphin-2, at doses of 3, 10 and 30 microg, i.c.v., dose-dependently inhibited the number of capsaicin-induced coughs. However, the same doses (3, 10 and 30 microg) of endomorphin-1 injected with i.c.v. had no significant effects on the number of capsaicin-induced coughs. The antitussive effect of endomorphin-2 was significantly reduced by beta-funaltrexamine, a mu(1)/mu(2)-opioid receptor antagonist, but not naloxonazine, a selective mu(1)-opioid receptor antagonist. Furthermore, the antitussive effect of endomorphin-2 was also partially but significantly reduced by nor-binaltorphimine, a selective kappa-opioid receptor antagonist. These results indicate that the administration of the endogenous mu-opioid ligand endomorphin-2, but not endomorphin-1, into the brain produces an antitussive effect via mainly naloxonazine-insensitive mu-opioid receptors, namely mu(2)-opioid receptors and partially kappa-opioid receptors.
Kamei
Junzo
J
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan. kamei@hoshi.ac.jp
Morita
Kayo
K
Saitoh
Akiyoshi
A
Nagase
Hiroshi
H
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology
D000996:Antitussive Agents; D009842:Oligopeptides; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D009270:Naloxone; C051844:norbinaltorphimine; C105294:endomorphin 2; D009271:Naltrexone; C024524:beta-funaltrexamine; C034643:naloxonazine; D002211:Capsaicin