Differential involvement of mu 1-opioid receptors in dermorphin tetrapeptide analogues-induced antinociception.
The involvement of putative mu(1)-opioid receptors in the antinociception induced by the dermorphin tetrapeptide analogues Try-D-Arg-Phe-beta-Ala (TAPA) and Tyr-D-Arg-Phe-beta-Ala-NH(2) (TAPA-NH(2)) was determined in mice, using a tail-pressure test and a formalin test. TAPA and TAPA-NH(2) injected i.c.v. and i.t. produced dose-dependent antinociception in both assays. In the tail-pressure test, the antinociception induced by i.c.v. or i.t. injected TAPA, but not TAPA-NH(2), was significantly attenuated by pretreatment with naloxonazine, a selective antagonist for putative mu(1)-opioid receptors. Moreover, naloxonazine also significantly attenuated the antinociception induced by i.c.v. injected TAPA, but not TAPA-NH(2), in the formalin test. In contrast, the antinociception induced by both TAPA and TAPA-NH(2) given i.t. was significantly attenuated by pretreatment with naloxonazine in the formalin test. The present results suggest that TAPA and TAPA-NH(2) should be considered selective agonists for putative mu(1)- and mu(2)-opioid receptors, respectively. The C-terminal amidation of TAPA-NH(2) may be critical for distinguishing between putative mu(1)- and mu(2)-opioid receptors.
Mizoguchi
Hirokazu
H
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Yuhki
Masayuki
M
Watanabe
Hiroyuki
H
Hayashi
Takafumi
T
Sakurada
Chikai
C
Yonezawa
Akihiko
A
Sakurada
Tsukasa
T
Sakurada
Shinobu
S
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D017450:Receptors, Opioid, mu / Q000502:physiology*
D000700:Analgesics; D009842:Oligopeptides; C404943:Oprm protein, mouse; D017450:Receptors, Opioid, mu; C059393:tyrosyl-arginyl-phenylalanyl-glycinamide; D009270:Naloxone; C034643:naloxonazine