Involvement of mouse μ-opioid receptor splice variants in the spinal antinociception induced by the dermorphin tetrapeptide analog amidino-TAPA.
The involvement of the mouse μ-opioid receptor (mMOR-1) splice variants in the antinociceptive effect of intrathecally (i.t.) administered N(α)-amidino-Tyr-D-Arg-Phe-β-Ala (amidino-TAPA) and [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO) was investigated in mice by monitoring the recovery from acute antinociceptive tolerance to amidino-TAPA and DAMGO. A single i.t. pretreatment with DAMGO produced an acute antinociceptive tolerance, which peaked at 2h and disappeared within 5h after the pretreatment. In contrast, a single i.t. pretreatment with amidino-TAPA produced an acute antinociceptive tolerance, which disappeared within 3h after the pretreatment. The concomitant i.t. pretreatment with an antisense oligodeoxynucleotide (ODN) for exon-1, exon-12, exon-13 or exon-14 of mMOR-1 maintained the acute antinociceptive tolerance to amidino-TAPA for 24h after the pretreatment. On the other hand, the concomitant i.t. pretreatment with an antisense ODN for exon-1 of mMOR-1, but not an antisense ODN for exon-12, exon-13 or exon-14 of mMOR-1, maintained the acute antinociceptive tolerance to DAMGO for 24h after the pretreatment. The present results suggest that the spinal antinociception of amidino-TAPA is partially mediated through the activation of the amidino-TAPA-sensitive and DAMGO-insensitive mMOR-1 splice variants MOR-1J, MOR-1K and MOR-1L, which contain the sequence encoded by exon-12, exon-13 and exon-14, respectively.
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
Hirokazu
H
Mizoguchi
Chizuko
C
Watanabe
Takayuki
T
Higashiya
Satoshi
S
Takeda
Kaori
K
Moriyama
Akihiko
A
Yonezawa
Takumi
T
Sato
Takaaki
T
Komatsu
Tsukasa
T
Sakurada
Shinobu
S
Sakurada
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005091:Exons / Q000235:genetics; D008297:Male; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D018847:Opioid Peptides / Q000737:chemistry*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism*
D000700:Analgesics; D020319:Oligodeoxyribonucleotides, Antisense; D009842:Oligopeptides; D018847:Opioid Peptides; D020033:Protein Isoforms; D017450:Receptors, Opioid, mu; C412736:tyrosyl-arginyl-phenylalanyl-beta--alanine; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C030058:dermorphin