Differential involvement of mu-opioid receptor subtypes in endomorphin-1- and -2-induced antinociception.
We investigated the role of mu-opioid receptor subtypes in both endomorphin-1 and endomorphin-2 induced antinociception in mice using supraspinally mediated behavior. With tail pressure as a mechanical noxious stimulus, both intracerebroventricularly (i.c.v.) and intrathecally (i.t.) injected-endomorphins produced potent and significant antinociceptive activity. Antinociception induced by i.t. and i.c.v. injection of endomorphin-1 was not reversed by pretreatment with a selective mu1-opioid receptor antagonist, naloxonazine (35 mg/kg, s.c.). By contrast, antinociception induced by i.t. and i.c.v. endomorphin-2 was significantly decreased by mu1-opioid receptor antagonist. Antinociception of both i.t. and i.c.v. endomorphin-1 and -2 was completely reversed by pretreatment with beta-funaltrexamine (40 mg/kg, s.c.). The results indicate that endomorphins may produce antinociception through the distinct mu1 and mu2 subtypes of mu-opioid receptor.
Sakurada
S
S
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, Sendai, Japan. s-sakura@tohoku-pharm.ac.jp
Zadina
J E
JE
Kastin
A J
AJ
Katsuyama
S
S
Fujimura
T
T
Murayama
K
K
Yuki
M
M
Ueda
H
H
Sakurada
T
T
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*; D013997:Time Factors
D000701:Analgesics, Opioid; D004745:Enkephalins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C105294:endomorphin 2; D009271:Naltrexone; C024524:beta-funaltrexamine; C034643:naloxonazine