title: Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone.
abstract: To determine if different subtypes of mu-opioid receptors were involved in antinociception induced by endomorphin-1 and endomorphin-2, the effect of pretreatment with various mu-opioid receptor antagonists beta-funaltrexamine, naloxonazine and 3-methylnaltrexone on the inhibition of the paw-withdrawal induced by endomorphin-1 and endomorphin-2 given intracerebroventricularly (i.c.v.) were studied in ddY male mice. The inhibition of the paw-withdrawal induced by i.c.v. administration of endomorphin-1, endomorphin-2 or DAMGO was completely blocked by the pretreatment with a selective mu-opioid receptor antagonist beta-funaltrexamine (40 mg/kg), indicating that the antinociception induced by all these peptides are mediated by the stimulation of mu-opioid receptors. However, naloxonazine, a mu1-opioid receptor antagonist pretreated s.c. for 24h was more effective in blocking the antinociception induced by endomorphin-2, than by endomorphin-1 or DAMGO given i.c.v. Pretreatment with a selective morphine-6 beta-glucuronide blocker 3-methylnaltrexone 0.25mg/kg given s.c. for 25 min or co-administration of 3-methylnaltrexone 2.5 ng given i.c.v. effectively attenuated the antinociception induced by endomorphin-2 given i.c.v. and co-administration of 3-methylnaltrexone shifted the dose-response curves for endomorphin-2 induced antinociception to the right by 4-fold. The administration of 3-methylnaltrexone did not affect the antinociception induced by endomorphin-1 or DAMGO given i.c.v. Our results indicate that the antinociception induced by endomorphin-2 is mediated by the stimulation of subtypes of mu-opioid receptor, which is different from that of mu-opioid receptor subtype stimulation by endomorphin-1 and DAMGO.
authors.affiliation: Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Sendai, Japan. s-sakura@tohoku-pharm.ac.jp
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
authors.forename: Takafumi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yuhki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujimura
authors.forename: Kimie
authors.initials: K
authors.lastname: Murayama
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yonezawa
authors.forename: Chikai
authors.initials: C
authors.lastname: Sakurada
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takeshita
authors.forename: Takumi
authors.initials: T
authors.lastname: Sato
authors.forename: James E
authors.initials: JE
authors.lastname: Zadina
authors.forename: Abba J
authors.initials: AJ
authors.lastname: Kastin
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sakurada
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D000644:Quaternary Ammonium Compounds; D012018:Reflex / Q000187:drug effects; D013997:Time Factors
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D000644:Quaternary Ammonium Compounds; C105293:endomorphin 1; C032257:methylnaltrexone; D009270:Naloxone; C105294:endomorphin 2; D009271:Naltrexone; C034643:naloxonazine