Contribution of spinal mu(1)-opioid receptors and dynorphin B to the antinociception induced by Tyr-d-Arg-Phe-Sar.
The antinociceptive effect of Tyr-d-Arg-Phe-Sar (TAPS) at the spinal level was characterized with the mouse tail-flick test. Intrathecal (i.t.) administration of TAPS produced a dose-dependent antinociception. The antinociception induced by TAPS was completely blocked by i.t. pretreatment with the mu-opioid receptor antagonist beta-funaltrexamine, the mu(1)-opioid receptor antagonist naloxonazine or the kappa-opioid receptor antagonist nor-binaltorphimine, but not with the delta-opioid receptor antagonist naltrindole. Moreover, TAPS-induced antinociception was dose-dependently attenuated by i.t. pretreatment with an antiserum against dynorphin B, but not against dynorphin A, alpha-neo-endorphin, [Met(5)]enkephalin, or [Leu(5)]enkephalin. In mice lacking prodynorphin, TAPS-induced antinociception was significantly reduced compared to that in wild-type mice. These results suggest that TAPS mainly stimulates mu(1)-opioid receptors, which subsequently induce the release of dynorphin B, which then acts on kappa-opioid receptors to produce antinociception.
Mizoguchi
Hirokazu
H
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Ito
Kanenori
K
Watanabe
Hiroyuki
H
Watanabe
Chizuko
C
Katsuyama
Sou
S
Fujimura
Tsutomu
T
Sakurada
Tsukasa
T
Sakurada
Shinobu
S
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004399:Dynorphins / Q000378:metabolism*; D004723:Endorphins / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D000701:Analgesics, Opioid; D004723:Endorphins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004399:Dynorphins; C036200:rimorphin; C053418:tyrosyl-arginyl-phenylalanyl-sarcosine