title: Distinct physiological role of amidino-TAPA-sensitive and DAMGO-insensitive μ-opioid receptor splice variants in the mouse spinal cord.
abstract: The physiological role of the distinct splice variants for cloned mouse μ-opioid receptor (mMOR-1), mMOR-1J, mMOR-1K and mMOR-1L, which are sensitive to N(α)-amidino-Tyr-D-Arg-Phe-β-Ala (amidino-TAPA) and insensitive to [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO), was described in the mouse spinal cord. The antinociception induced by intrathecally (i.t.) injected amidino-TAPA was attenuated by i.t. pretreatment with antisera against the endogenous opioid peptides dynorphin A, dynorphin B, α-neo-endorphin, or [Leu(5)]enkephalin in naïve mice. However, in mice whose spinal mMOR-1J had been knocked-down using the antisense oligodeoxynucleotide (ODN) for exon-12 of mMOR-1 gene, the inhibiting effect of antiserum against dynorphin A on amidino-TAPA-induced antinociception was eliminated. In contrast, the inhibiting effect of antisera against dynorphin B or α-neo-endorphin on amidino-TAPA-induced antinociception was eliminated in mice whose spinal mMOR-1K had been knocked-down using the antisense ODN for exon-13 of mMOR-1 gene. Moreover, the inhibiting effect of antisera against dynorphin A or [Leu(5)]enkephalin on amidino-TAPA-induced antinociception was eliminated in mice whose spinal mMOR-1L had been knocked-down using the antisense ODN for exon-14 of mMOR-1 gene. The present results suggest that the distinct antinociceptive profile of amidino-TAPA, that is the release of endogenous κ- and δ-opioid peptides in spinal cord, is mediated through the activation of mMOR-1J, mMOR-1K or mMOR-1L, which contain the sequence encoded by exon-12, exon-13 or exon-14 of mMOR-1 gene, respectively.
authors.affiliation: Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Sendai 981-8558, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Chizuko
authors.initials: C
authors.lastname: Watanabe
authors.forename: Takayuki
authors.initials: T
authors.lastname: Higashiya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeda
authors.forename: Kaori
authors.initials: K
authors.lastname: Moriyama
authors.forename: Yuta
authors.initials: Y
authors.lastname: Aoki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kon-no
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takagi
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: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000700:Analgesics; C520058:N(alpha)-amidino-Tyr-D-Arg-Phe-beta-Ala; D009842:Oligopeptides; D020033:Protein Isoforms; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-