Effects of nitric oxide synthase inhibitors on N-methyl-d-aspartate-induced phase delay of circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro

Akihito Watanabe, Toshiyuki Hamada, Shigenobu Shibata, Shigenori Watanabe

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Excitatory amino acid (EAA) receptors such as N-methyl-d-aspartate (NMDA) and non-NMDA receptors have been suggested to play an important role in the regulation of photic information from the retina to the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of glutamate as a retinohypothalamic transmitter by analyzing the phase-resetting effects of NMDA and a non-NMDA agonist, (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), on the circadian rhythm of SCN firing activity. Nitric oxide (NO) production is believed to be an essential intermediate in NMDA-induced cGMP production in the CNS. Thus, we examined the effects of blockers of NO production on NMDA- or AMPA-induced phase delay of SCN activity rhythm. N-nitro-l-arginine methylester (l-NAME) blocked NMDA- but not AMPA-induced phase shift, indicating the involvement of NO synthesis in NMDA-induced phase changes. l-arginine but not d-arginine caused a phase delay, and l-NAME blocked l-arginine-induced phase delay. In addition, cotreatment with NMDA and l-arginine did not have an additive effect. These results suggest that NO production itself is involved in the phase change of SCN neuron activity, and NMDA-induced phase changes are also mediated via activation of NO synthesis in this nucleus.

Original languageEnglish
Pages (from-to)161-164
Number of pages4
JournalBrain Research
Volume646
Issue number1
DOIs
Publication statusPublished - 1994 May 16
Externally publishedYes

Fingerprint

Suprachiasmatic Nucleus
Circadian Rhythm
Aspartic Acid
Nitric Oxide Synthase
Nitric Oxide
Arginine
In Vitro Techniques
Glutamate Receptors
Retina
Glutamic Acid
Neurons

Keywords

  • Circadian rhythm
  • Nitric oxide
  • NMDA
  • Retinohypothalamic tract
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Effects of nitric oxide synthase inhibitors on N-methyl-d-aspartate-induced phase delay of circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro. / Watanabe, Akihito; Hamada, Toshiyuki; Shibata, Shigenobu; Watanabe, Shigenori.

In: Brain Research, Vol. 646, No. 1, 16.05.1994, p. 161-164.

Research output: Contribution to journalArticle

@article{300bbe6bd4fc4578a197e5824d2b49e8,
title = "Effects of nitric oxide synthase inhibitors on N-methyl-d-aspartate-induced phase delay of circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro",
abstract = "Excitatory amino acid (EAA) receptors such as N-methyl-d-aspartate (NMDA) and non-NMDA receptors have been suggested to play an important role in the regulation of photic information from the retina to the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of glutamate as a retinohypothalamic transmitter by analyzing the phase-resetting effects of NMDA and a non-NMDA agonist, (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), on the circadian rhythm of SCN firing activity. Nitric oxide (NO) production is believed to be an essential intermediate in NMDA-induced cGMP production in the CNS. Thus, we examined the effects of blockers of NO production on NMDA- or AMPA-induced phase delay of SCN activity rhythm. N-nitro-l-arginine methylester (l-NAME) blocked NMDA- but not AMPA-induced phase shift, indicating the involvement of NO synthesis in NMDA-induced phase changes. l-arginine but not d-arginine caused a phase delay, and l-NAME blocked l-arginine-induced phase delay. In addition, cotreatment with NMDA and l-arginine did not have an additive effect. These results suggest that NO production itself is involved in the phase change of SCN neuron activity, and NMDA-induced phase changes are also mediated via activation of NO synthesis in this nucleus.",
keywords = "Circadian rhythm, Nitric oxide, NMDA, Retinohypothalamic tract, Suprachiasmatic nucleus",
author = "Akihito Watanabe and Toshiyuki Hamada and Shigenobu Shibata and Shigenori Watanabe",
year = "1994",
month = "5",
day = "16",
doi = "10.1016/0006-8993(94)90071-X",
language = "English",
volume = "646",
pages = "161--164",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Effects of nitric oxide synthase inhibitors on N-methyl-d-aspartate-induced phase delay of circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro

AU - Watanabe, Akihito

AU - Hamada, Toshiyuki

AU - Shibata, Shigenobu

AU - Watanabe, Shigenori

PY - 1994/5/16

Y1 - 1994/5/16

N2 - Excitatory amino acid (EAA) receptors such as N-methyl-d-aspartate (NMDA) and non-NMDA receptors have been suggested to play an important role in the regulation of photic information from the retina to the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of glutamate as a retinohypothalamic transmitter by analyzing the phase-resetting effects of NMDA and a non-NMDA agonist, (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), on the circadian rhythm of SCN firing activity. Nitric oxide (NO) production is believed to be an essential intermediate in NMDA-induced cGMP production in the CNS. Thus, we examined the effects of blockers of NO production on NMDA- or AMPA-induced phase delay of SCN activity rhythm. N-nitro-l-arginine methylester (l-NAME) blocked NMDA- but not AMPA-induced phase shift, indicating the involvement of NO synthesis in NMDA-induced phase changes. l-arginine but not d-arginine caused a phase delay, and l-NAME blocked l-arginine-induced phase delay. In addition, cotreatment with NMDA and l-arginine did not have an additive effect. These results suggest that NO production itself is involved in the phase change of SCN neuron activity, and NMDA-induced phase changes are also mediated via activation of NO synthesis in this nucleus.

AB - Excitatory amino acid (EAA) receptors such as N-methyl-d-aspartate (NMDA) and non-NMDA receptors have been suggested to play an important role in the regulation of photic information from the retina to the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of glutamate as a retinohypothalamic transmitter by analyzing the phase-resetting effects of NMDA and a non-NMDA agonist, (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), on the circadian rhythm of SCN firing activity. Nitric oxide (NO) production is believed to be an essential intermediate in NMDA-induced cGMP production in the CNS. Thus, we examined the effects of blockers of NO production on NMDA- or AMPA-induced phase delay of SCN activity rhythm. N-nitro-l-arginine methylester (l-NAME) blocked NMDA- but not AMPA-induced phase shift, indicating the involvement of NO synthesis in NMDA-induced phase changes. l-arginine but not d-arginine caused a phase delay, and l-NAME blocked l-arginine-induced phase delay. In addition, cotreatment with NMDA and l-arginine did not have an additive effect. These results suggest that NO production itself is involved in the phase change of SCN neuron activity, and NMDA-induced phase changes are also mediated via activation of NO synthesis in this nucleus.

KW - Circadian rhythm

KW - Nitric oxide

KW - NMDA

KW - Retinohypothalamic tract

KW - Suprachiasmatic nucleus

UR - http://www.scopus.com/inward/record.url?scp=0028199612&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028199612&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(94)90071-X

DO - 10.1016/0006-8993(94)90071-X

M3 - Article

VL - 646

SP - 161

EP - 164

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -