title: Involvement of spinal release of α-neo-endorphin on the antinociceptive effect of TAPA.
abstract: The antinociceptive effect of i.t.-administered Tyr-d-Arg-Phe-β-Ala (TAPA), an N-terminal tetrapeptide analog of dermorphin, was characterized in ddY mice. In the mouse tail-flick test, TAPA administered i.t. produced a potent antinociception. The antinociception induced by TAPA was significantly attenuated by i.t. pretreatment with the κ-opioid receptor antagonist nor-binaltorphimine, as well as by the μ-opioid receptor antagonist β-funaltrexamine and the μ1-opioid receptor antagonist naloxonazine. TAPA-induced antinociception was also significantly suppressed by co-administration of the μ1-opioid receptor antagonist Tyr-d-Pro-Phe-Phe-NH2 (d-Pro(2)-endomorphin-2) but not by co-administration of the μ2-opioid receptor antagonists Tyr-d-Pro-Trp-Phe-NH2 (d-Pro(2)-endomorphin-1) and Tyr-d-Pro-Trp-Gly-NH2 (d-Pro(2)-Tyr-W-MIF-1). In CXBK mice whose μ1-opioid receptors were naturally reduced, the antinociceptive effect of TAPA was markedly suppressed compared to the parental strain C57BL/6ByJ mice. Moreover, the antinociception induced by TAPA was significantly attenuated by i.t. pretreatment with antiserum against the endogenous κ-opioid peptide α-neo-endorphin but not antisera against other endogenous opioid peptides. In prodynorphin-deficient mice, the antinociceptive effect of TAPA was significantly reduced compared to wild-type mice. These results suggest that the spinal antinociception induced by TAPA is mediated in part through the release of α-neo-endorphin in the spinal cord via activation of spinal μ1-opioid receptors.
authors.affiliation: Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kon-No
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Chizuko
authors.initials: C
authors.lastname: Watanabe
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yonezawa
authors.forename: Takumi
authors.initials: T
authors.lastname: Sato
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sakurada
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
mesh_terms: D000698:Analgesia / Q000523:psychology; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D000818:Animals; D004723:Endorphins / Q000096:biosynthesis / Q000378:metabolism; D015870:Gene Expression; D007106:Immune Sera / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D059225:Nociception / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013623:Tail / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D004723:Endorphins; D007106:Immune Sera; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C412620:prolyl(2)-endomorphin-2; C412736:tyrosyl-arginyl-phenylalanyl-beta--alanine; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C025681:alpha-neoendorphin; C024524:beta-funaltrexamine; C034643:naloxonazine
keywords: Antinociception; Release; Spinal cord; TAPA; α-Neo-endorphin; μ-Opioid receptor