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The Journal of Neuroscience, March 15, 1999, 19(6):2152-2160
Orphanin-FQ/Nociceptin (OFQ/N) Modulates the Activity of
Suprachiasmatic Nucleus Neurons
Charles N.
Allen1, 2,
Zhi-Gen
Jiang1,
Koji
Teshima1,
Tristan
Darland3,
Masayuki
Ikeda5,
Cole S.
Nelson1,
Denise I.
Quigley4,
Tohru
Yoshioka5,
Richard G.
Allen1,
Michael A.
Rea6, and
David K.
Grandy2, 3
1 Center for Research on Occupational and Environmental
Toxicology and Departments of 2 Physiology and
Pharmacology, 3 Cell and Developmental Biology, and
4 Molecular and Medical Genetics, Oregon Health Sciences
University, Portland, Oregon 97201-3098, 5 Department of
Molecular Neurobiology, School of Human Sciences, Waseda University,
Mikajima, Tokorozawa, Saitama 359, Japan, and
6 Biological Rhythms and Integrative Neurosciences Research
Institute, Air Force Research Laboratory, Brooks Air Force Base, Texas
78235
Neurons in the suprachiasmatic nucleus (SCN) constitute the
principal circadian pacemaker of mammals. In situ
hybridization studies revealed expression of
orphanin-FQ/nociceptin (OFQ/N) receptor (NOR) mRNA in the SCN,
whereas no expression of mRNA for preproOFQ/N (ppOFQ/N) was detected.
The presence of OFQ/N peptide in the SCN was demonstrated by
radioimmunoassay. SCN neurons (88%) responded dose-dependently to
OFQ/N with an outward current (EC50 = 22.3 nM) that was reduced in amplitude by membrane
hyperpolarization and reversed polarity near the theoretical potassium
equilibrium potential.
[Phe1 (Ch2-NH)Gly2]OFQ/N(1-13)NH2
(3 µM), a putative NOR antagonist, activated a small
outward current and significantly reduced the amplitude of the
OFQ/N-stimulated current. OFQ/N reduced the NMDA receptor-mediated increase in intracellular Ca2+. When injected
unilaterally into the SCN of Syrian hamsters housed in constant
darkness, OFQ/N (1-50 pmol) failed to alter the timing of the
hamsters' wheel-running activity. However, injection of OFQ/N (0.1-50
pmol) before a brief exposure to light during the midsubjective night
significantly attenuated the light-induced phase advances of the
activity rhythm. These data are consistent with the interpretation that
OFQ/N acting at specific receptors modulates the activity of SCN
neurons and, thereby, the response of the circadian clock to light.
Key words:
orphanin-FQ; nociceptin; suprachiasmatic nucleus; circadian rhythm; potassium current; calcium
Copyright © 1999 Society for Neuroscience 0270-6474/99/1962152-09$05.00/0
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