Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin receptor-knockout mice

Yukihiro Noda, Takayoshi Mamiya, Toshitaka Nabeshima, Miyuki Nishi, Masaya Higashioka, Hiroshi Takeshima

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Nociceptin and nociceptin receptor, which show structural similarities to opioid peptides and opioid receptors, respectively, have been recently found to constitute a novel neuromodulatory system. In the brain, however, the physiological role of the modulation via the nociceptin receptor is still unclear. Administered nociceptin produces hyperalgesia and hypolocomotion, whereas the nociceptin receptor-knockout mice show no significant abnormalities in nociceptive thresholds and locomotion. To clarify possible involvement of the nociceptin receptor in the regulation of nociception and locomotion, we made use of the knockout mice and naloxone benzoylhydrazone (NalBzoH) identified originally as a ligand for opioid receptors. Experiments on the cultured cells transfected with the nociceptin receptor cDNA showed that NalBzoH competed with [3H]nociceptin binding and attenuated the nociceptin-induced inhibition of cAMP accumulation. Furthermore, behavioral studies demonstrated that NalBzoH completely inhibited nociceptin-induced hyperalgesia and hypolocomotion. It is therefore likely that NalBzoH can act as a potent antagonist for the nociceptin receptor in vivo. In wild-type mice, NalBzoH induced antinociception but did not affect locomotor activity. In contrast, in the knockout mice, no significant changes in nociception and locomotion were induced by NalBzoH. These results clearly suggest that the nociceptin system takes part in the physiological regulation of nociceptive thresholds but not in the basal modulation of locomotion.

Original languageEnglish
Pages (from-to)18047-18051
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number29
DOIs
Publication statusPublished - 17-07-1998
Externally publishedYes

Fingerprint

Knockout Mice
Locomotion
Nociception
Hyperalgesia
Opioid Receptors
Modulation
Peptide Receptors
Opioid Peptides
nociceptin receptor
nociceptin
naloxone benzoylhydrazone
Cultured Cells
Brain
Complementary DNA
Cells
Ligands
Experiments

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Noda, Yukihiro ; Mamiya, Takayoshi ; Nabeshima, Toshitaka ; Nishi, Miyuki ; Higashioka, Masaya ; Takeshima, Hiroshi. / Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin receptor-knockout mice. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 29. pp. 18047-18051.
@article{bbf6098ab74743efa111e221ac43c3e7,
title = "Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin receptor-knockout mice",
abstract = "Nociceptin and nociceptin receptor, which show structural similarities to opioid peptides and opioid receptors, respectively, have been recently found to constitute a novel neuromodulatory system. In the brain, however, the physiological role of the modulation via the nociceptin receptor is still unclear. Administered nociceptin produces hyperalgesia and hypolocomotion, whereas the nociceptin receptor-knockout mice show no significant abnormalities in nociceptive thresholds and locomotion. To clarify possible involvement of the nociceptin receptor in the regulation of nociception and locomotion, we made use of the knockout mice and naloxone benzoylhydrazone (NalBzoH) identified originally as a ligand for opioid receptors. Experiments on the cultured cells transfected with the nociceptin receptor cDNA showed that NalBzoH competed with [3H]nociceptin binding and attenuated the nociceptin-induced inhibition of cAMP accumulation. Furthermore, behavioral studies demonstrated that NalBzoH completely inhibited nociceptin-induced hyperalgesia and hypolocomotion. It is therefore likely that NalBzoH can act as a potent antagonist for the nociceptin receptor in vivo. In wild-type mice, NalBzoH induced antinociception but did not affect locomotor activity. In contrast, in the knockout mice, no significant changes in nociception and locomotion were induced by NalBzoH. These results clearly suggest that the nociceptin system takes part in the physiological regulation of nociceptive thresholds but not in the basal modulation of locomotion.",
author = "Yukihiro Noda and Takayoshi Mamiya and Toshitaka Nabeshima and Miyuki Nishi and Masaya Higashioka and Hiroshi Takeshima",
year = "1998",
month = "7",
day = "17",
doi = "10.1074/jbc.273.29.18047",
language = "English",
volume = "273",
pages = "18047--18051",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "29",

}

Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin receptor-knockout mice. / Noda, Yukihiro; Mamiya, Takayoshi; Nabeshima, Toshitaka; Nishi, Miyuki; Higashioka, Masaya; Takeshima, Hiroshi.

In: Journal of Biological Chemistry, Vol. 273, No. 29, 17.07.1998, p. 18047-18051.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin receptor-knockout mice

AU - Noda, Yukihiro

AU - Mamiya, Takayoshi

AU - Nabeshima, Toshitaka

AU - Nishi, Miyuki

AU - Higashioka, Masaya

AU - Takeshima, Hiroshi

PY - 1998/7/17

Y1 - 1998/7/17

N2 - Nociceptin and nociceptin receptor, which show structural similarities to opioid peptides and opioid receptors, respectively, have been recently found to constitute a novel neuromodulatory system. In the brain, however, the physiological role of the modulation via the nociceptin receptor is still unclear. Administered nociceptin produces hyperalgesia and hypolocomotion, whereas the nociceptin receptor-knockout mice show no significant abnormalities in nociceptive thresholds and locomotion. To clarify possible involvement of the nociceptin receptor in the regulation of nociception and locomotion, we made use of the knockout mice and naloxone benzoylhydrazone (NalBzoH) identified originally as a ligand for opioid receptors. Experiments on the cultured cells transfected with the nociceptin receptor cDNA showed that NalBzoH competed with [3H]nociceptin binding and attenuated the nociceptin-induced inhibition of cAMP accumulation. Furthermore, behavioral studies demonstrated that NalBzoH completely inhibited nociceptin-induced hyperalgesia and hypolocomotion. It is therefore likely that NalBzoH can act as a potent antagonist for the nociceptin receptor in vivo. In wild-type mice, NalBzoH induced antinociception but did not affect locomotor activity. In contrast, in the knockout mice, no significant changes in nociception and locomotion were induced by NalBzoH. These results clearly suggest that the nociceptin system takes part in the physiological regulation of nociceptive thresholds but not in the basal modulation of locomotion.

AB - Nociceptin and nociceptin receptor, which show structural similarities to opioid peptides and opioid receptors, respectively, have been recently found to constitute a novel neuromodulatory system. In the brain, however, the physiological role of the modulation via the nociceptin receptor is still unclear. Administered nociceptin produces hyperalgesia and hypolocomotion, whereas the nociceptin receptor-knockout mice show no significant abnormalities in nociceptive thresholds and locomotion. To clarify possible involvement of the nociceptin receptor in the regulation of nociception and locomotion, we made use of the knockout mice and naloxone benzoylhydrazone (NalBzoH) identified originally as a ligand for opioid receptors. Experiments on the cultured cells transfected with the nociceptin receptor cDNA showed that NalBzoH competed with [3H]nociceptin binding and attenuated the nociceptin-induced inhibition of cAMP accumulation. Furthermore, behavioral studies demonstrated that NalBzoH completely inhibited nociceptin-induced hyperalgesia and hypolocomotion. It is therefore likely that NalBzoH can act as a potent antagonist for the nociceptin receptor in vivo. In wild-type mice, NalBzoH induced antinociception but did not affect locomotor activity. In contrast, in the knockout mice, no significant changes in nociception and locomotion were induced by NalBzoH. These results clearly suggest that the nociceptin system takes part in the physiological regulation of nociceptive thresholds but not in the basal modulation of locomotion.

UR - http://www.scopus.com/inward/record.url?scp=0032541091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032541091&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.29.18047

DO - 10.1074/jbc.273.29.18047

M3 - Article

C2 - 9660760

AN - SCOPUS:0032541091

VL - 273

SP - 18047

EP - 18051

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 29

ER -