Differentiation of opioid receptor preference by [Dmt1]endomorphin-2-mediated antinociception in the mouse.
The potent opioid [Dmt1]endomorphin-2 (Dmt-Pro-Phe-Phe-NH2) differentiated between the opioid receptor subtypes responsible for the antinociception elicited by endomorphin-2 in mice. Antinociception, induced by the intracerebroventricular administration of [Dmt1]endomorphin-2 and inhibited by various opioid receptor antagonists [naloxone, naltrindole, beta-funaltrexamine, naloxonazine], was determined by the tail-flick (spinal effect) and hot-plate (supraspinal effect) tests. The opioid receptor subtypes involved in [Dmt1]endomorphin-2-induced antinociception differed between these in vivo model paradigms: naloxone (non-specific opioid receptor antagonist) and beta-funaltrexamine (irreversible mu1/mu2-opioid receptor antagonist) blocked antinociception in both tests, although stronger inhibition occurred in the hot-plate than the tail-flick test suggesting involvement of other opioid receptors. Consequently, we applied naloxonazine (mu1-opioid receptor antagonist) that significantly blocked the effect in the hot-plate test and naltrindole (delta-opioid receptor antagonist), which was only effective in the tail-flick test. The data indicated that [Dmt1]endomorphin-2-induced spinal antinociception was primarily mediated by both mu2- and delta-opioid receptors, while a supraspinal mechanism involved only mu1/mu2-subtypes.
Jinsmaa
Yunden
Y
Medicinal Chemistry Group, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. yunden@niehs.nih.gov
Fujita
Yoshio
Y
Shiotani
Kimitaka
K
Miyazaki
Anna
A
Li
Tingyou
T
Tsuda
Yuko
Y
Okada
Yoshio
Y
Ambo
Akihiro
A
Sasaki
Yusuke
Y
Bryant
Sharon D
SD
Lazarus
Lawrence H
LH
D000698:Analgesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006358:Hot Temperature / Q000009:adverse effects; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D009619:Nociceptors / Q000187:drug effects; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D010146:Pain; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017465:Receptors, Opioid, delta / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000502:physiology; D013623:Tail; D013997:Time Factors
D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; C105294:endomorphin 2; D009271:Naltrexone; C024524:beta-funaltrexamine; C034643:naloxonazine; C055382:naltrindole