title: Endomorphin analogues containing D-Pro2 discriminate different mu-opioid receptor mediated antinociception in mice.
abstract: The antagonistic actions of D-Pro(2)-endomorphins on inhibition of the paw withdrawal response by endomorphins were studied in mice. D-Pro(2)-endomorphin-1 and D-Pro(2)-endomorphin-2, injected intrathecally (i.t.), had no significant effect on the nociceptive thermal threshold alone. When D-Pro(2)-endomorphin-1 (0.05-0.1 pmol) was injected simultaneously with i.t. endomorphin-1 (5.0 nmol) or endomorphin-2 (5.0 nmol), antinociception induced by endomoprhin-1 was reduced significantly, whereas endomorphin-2-induced antinociception was not affected by D-Pro(2)-endomorphin-1. Antinociception induced by i.t. endomorphin-2 (5.0 nmol) was reduced significantly by its analogue, D-Pro(2)-endomorphin-2 (100 pmol), but not by D-Pro(2)-endomorphin-1. D-Pro(2)-endomorphin-1. D-Pro(2)-endomorphin-1 also antagonized the antinociceptive effect of i.t. DAMGO, a mu-opioid receptor agonist, whereas D-Pro(2)-endomorphin-2 failed to reduce the effect of DAMGO. These results suggest that endomorphin analogues containing D-Pro(2) are able to discriminate the antinociceptive actions of mu(1)- and mu(2)-opioid receptor agonists at the spinal cord level.
authors.affiliation: Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatushima, Sendai 981-8558, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
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: Chikai
authors.initials: C
authors.lastname: Sakurada
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sakurada
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C412620:prolyl(2)-endomorphin-2; C105294:endomorphin 2