Nonphotic entrainment of the circadian body temperature rhythm by the selective ORL1 receptor agonist W-212393 in rats

Koji Teshima, Masanori Minoguchi, Sayuri Tounai, Atsuyuki Ashimori, Junichi Eguchi, Charles Allen, Shigenobu Shibata

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We synthesized a small-molecule opioid receptor-like 1 (ORL1) receptor agonist, 2-{3-[1-((1R)-acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo- benzimidazol-1-yl}-N-methylacetamide (W-212393), and investigated its effect on the circadian body temperature rhythm of rats. W-212393 has high affinity for ORL1 receptors in the rat cerebral cortex and human ORL1 receptors expressed in HEK293 cells with K i values of 0.76 and 0.50 nM, respectively. W-212393 concentration-dependently stimulated GTPγ 35S binding and its efficacy was similar to nociceptin/orphanin FQ (N/OFQ), suggesting that W-212393 is a full agonist at ORL1 receptors. W-212393 dose-dependently occupied ORL1 receptors following intraventricular or intraperitoneal administration, suggesting that W-212393 is a brain-penetrating compound. W-212393 (100nM) and N/OFQ (100nM) significantly suppressed the activity of spontaneously firing rat suprachiasmatic nucleus neurons. These suppressive effects were blocked by an ORL1 receptor antagonist, J-113397 (1 μM). W-212393 (3 mg kg -1, i.p.) induced a significant phase advance at circadian time 6 (CT6) and CT9, but not at other CTs. The magnitude of the W-212393 (0.3-3 mg kg -1, i.p.)-induced phase advance was dose-dependent and greater than those produced by 8-hydroxy-2-(di-n-propylamino)tetralin (0.3-3 mg kg -1, i.p.) or melatonin (0.3-3 mg kg -1, i.p.). The W-212393 (3 mgkg -1, i.p.)-induced phase advance was antagonized by J-113397 (10 mg kg -1, i.p.). W-212393 (3 mg kg -1, i.p.) significantly accelerated the re-entrainment of the body temperature rhythm to a 6 h advanced light-dark cycle. These results indicate that activation of ORL1 receptors contributes to the circadian entrainment and W-212393 may represent an interesting agent for the study of circadian rhythms.

Original languageEnglish (US)
Pages (from-to)33-40
Number of pages8
JournalBritish Journal of Pharmacology
Volume146
Issue number1
DOIs
StatePublished - 2005

Fingerprint

Opioid Receptors
Body Temperature
2-(3-(1-(acenaphthen-1-yl)piperidin-4-yl)-2,3-dihydro-2-oxobenzimidazol-1-yl)-N-methylacetamide
8-Hydroxy-2-(di-n-propylamino)tetralin
Suprachiasmatic Nucleus
HEK293 Cells
Photoperiod
Melatonin
Circadian Rhythm
Guanosine Triphosphate
Cerebral Cortex
Neurons

Keywords

  • Circadian rhythm
  • Nociceptin
  • Nonphotic entrainment
  • ORL1
  • Orphanin FQ
  • SCN
  • W-212393

ASJC Scopus subject areas

  • Pharmacology

Cite this

Nonphotic entrainment of the circadian body temperature rhythm by the selective ORL1 receptor agonist W-212393 in rats. / Teshima, Koji; Minoguchi, Masanori; Tounai, Sayuri; Ashimori, Atsuyuki; Eguchi, Junichi; Allen, Charles; Shibata, Shigenobu.

In: British Journal of Pharmacology, Vol. 146, No. 1, 2005, p. 33-40.

Research output: Contribution to journalArticle

Teshima, Koji ; Minoguchi, Masanori ; Tounai, Sayuri ; Ashimori, Atsuyuki ; Eguchi, Junichi ; Allen, Charles ; Shibata, Shigenobu. / Nonphotic entrainment of the circadian body temperature rhythm by the selective ORL1 receptor agonist W-212393 in rats. In: British Journal of Pharmacology. 2005 ; Vol. 146, No. 1. pp. 33-40.
@article{53bc2965d53b449bbc26af6a22f6b7f5,
title = "Nonphotic entrainment of the circadian body temperature rhythm by the selective ORL1 receptor agonist W-212393 in rats",
abstract = "We synthesized a small-molecule opioid receptor-like 1 (ORL1) receptor agonist, 2-{3-[1-((1R)-acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo- benzimidazol-1-yl}-N-methylacetamide (W-212393), and investigated its effect on the circadian body temperature rhythm of rats. W-212393 has high affinity for ORL1 receptors in the rat cerebral cortex and human ORL1 receptors expressed in HEK293 cells with K i values of 0.76 and 0.50 nM, respectively. W-212393 concentration-dependently stimulated GTPγ 35S binding and its efficacy was similar to nociceptin/orphanin FQ (N/OFQ), suggesting that W-212393 is a full agonist at ORL1 receptors. W-212393 dose-dependently occupied ORL1 receptors following intraventricular or intraperitoneal administration, suggesting that W-212393 is a brain-penetrating compound. W-212393 (100nM) and N/OFQ (100nM) significantly suppressed the activity of spontaneously firing rat suprachiasmatic nucleus neurons. These suppressive effects were blocked by an ORL1 receptor antagonist, J-113397 (1 μM). W-212393 (3 mg kg -1, i.p.) induced a significant phase advance at circadian time 6 (CT6) and CT9, but not at other CTs. The magnitude of the W-212393 (0.3-3 mg kg -1, i.p.)-induced phase advance was dose-dependent and greater than those produced by 8-hydroxy-2-(di-n-propylamino)tetralin (0.3-3 mg kg -1, i.p.) or melatonin (0.3-3 mg kg -1, i.p.). The W-212393 (3 mgkg -1, i.p.)-induced phase advance was antagonized by J-113397 (10 mg kg -1, i.p.). W-212393 (3 mg kg -1, i.p.) significantly accelerated the re-entrainment of the body temperature rhythm to a 6 h advanced light-dark cycle. These results indicate that activation of ORL1 receptors contributes to the circadian entrainment and W-212393 may represent an interesting agent for the study of circadian rhythms.",
keywords = "Circadian rhythm, Nociceptin, Nonphotic entrainment, ORL1, Orphanin FQ, SCN, W-212393",
author = "Koji Teshima and Masanori Minoguchi and Sayuri Tounai and Atsuyuki Ashimori and Junichi Eguchi and Charles Allen and Shigenobu Shibata",
year = "2005",
doi = "10.1038/sj.bjp.0706311",
language = "English (US)",
volume = "146",
pages = "33--40",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Nonphotic entrainment of the circadian body temperature rhythm by the selective ORL1 receptor agonist W-212393 in rats

AU - Teshima, Koji

AU - Minoguchi, Masanori

AU - Tounai, Sayuri

AU - Ashimori, Atsuyuki

AU - Eguchi, Junichi

AU - Allen, Charles

AU - Shibata, Shigenobu

PY - 2005

Y1 - 2005

N2 - We synthesized a small-molecule opioid receptor-like 1 (ORL1) receptor agonist, 2-{3-[1-((1R)-acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo- benzimidazol-1-yl}-N-methylacetamide (W-212393), and investigated its effect on the circadian body temperature rhythm of rats. W-212393 has high affinity for ORL1 receptors in the rat cerebral cortex and human ORL1 receptors expressed in HEK293 cells with K i values of 0.76 and 0.50 nM, respectively. W-212393 concentration-dependently stimulated GTPγ 35S binding and its efficacy was similar to nociceptin/orphanin FQ (N/OFQ), suggesting that W-212393 is a full agonist at ORL1 receptors. W-212393 dose-dependently occupied ORL1 receptors following intraventricular or intraperitoneal administration, suggesting that W-212393 is a brain-penetrating compound. W-212393 (100nM) and N/OFQ (100nM) significantly suppressed the activity of spontaneously firing rat suprachiasmatic nucleus neurons. These suppressive effects were blocked by an ORL1 receptor antagonist, J-113397 (1 μM). W-212393 (3 mg kg -1, i.p.) induced a significant phase advance at circadian time 6 (CT6) and CT9, but not at other CTs. The magnitude of the W-212393 (0.3-3 mg kg -1, i.p.)-induced phase advance was dose-dependent and greater than those produced by 8-hydroxy-2-(di-n-propylamino)tetralin (0.3-3 mg kg -1, i.p.) or melatonin (0.3-3 mg kg -1, i.p.). The W-212393 (3 mgkg -1, i.p.)-induced phase advance was antagonized by J-113397 (10 mg kg -1, i.p.). W-212393 (3 mg kg -1, i.p.) significantly accelerated the re-entrainment of the body temperature rhythm to a 6 h advanced light-dark cycle. These results indicate that activation of ORL1 receptors contributes to the circadian entrainment and W-212393 may represent an interesting agent for the study of circadian rhythms.

AB - We synthesized a small-molecule opioid receptor-like 1 (ORL1) receptor agonist, 2-{3-[1-((1R)-acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo- benzimidazol-1-yl}-N-methylacetamide (W-212393), and investigated its effect on the circadian body temperature rhythm of rats. W-212393 has high affinity for ORL1 receptors in the rat cerebral cortex and human ORL1 receptors expressed in HEK293 cells with K i values of 0.76 and 0.50 nM, respectively. W-212393 concentration-dependently stimulated GTPγ 35S binding and its efficacy was similar to nociceptin/orphanin FQ (N/OFQ), suggesting that W-212393 is a full agonist at ORL1 receptors. W-212393 dose-dependently occupied ORL1 receptors following intraventricular or intraperitoneal administration, suggesting that W-212393 is a brain-penetrating compound. W-212393 (100nM) and N/OFQ (100nM) significantly suppressed the activity of spontaneously firing rat suprachiasmatic nucleus neurons. These suppressive effects were blocked by an ORL1 receptor antagonist, J-113397 (1 μM). W-212393 (3 mg kg -1, i.p.) induced a significant phase advance at circadian time 6 (CT6) and CT9, but not at other CTs. The magnitude of the W-212393 (0.3-3 mg kg -1, i.p.)-induced phase advance was dose-dependent and greater than those produced by 8-hydroxy-2-(di-n-propylamino)tetralin (0.3-3 mg kg -1, i.p.) or melatonin (0.3-3 mg kg -1, i.p.). The W-212393 (3 mgkg -1, i.p.)-induced phase advance was antagonized by J-113397 (10 mg kg -1, i.p.). W-212393 (3 mg kg -1, i.p.) significantly accelerated the re-entrainment of the body temperature rhythm to a 6 h advanced light-dark cycle. These results indicate that activation of ORL1 receptors contributes to the circadian entrainment and W-212393 may represent an interesting agent for the study of circadian rhythms.

KW - Circadian rhythm

KW - Nociceptin

KW - Nonphotic entrainment

KW - ORL1

KW - Orphanin FQ

KW - SCN

KW - W-212393

UR - http://www.scopus.com/inward/record.url?scp=28444485374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28444485374&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0706311

DO - 10.1038/sj.bjp.0706311

M3 - Article

VL - 146

SP - 33

EP - 40

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 1

ER -