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Contribution of spinal mu(1)-opioid receptors and dynorphin B to the antinociception induced by Tyr-d-Arg-Phe-Sar
Authors:Mizoguchi Hirokazu  Ito Kanenori  Watanabe Hiroyuki  Watanabe Chizuko  Katsuyama Sou  Fujimura Tsutomu  Sakurada Tsukasa  Sakurada Shinobu
Institution:Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Abstract: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.
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