The gut-brain peptide neuromedin U is involved in the mammalian circadian oscillator system.
Immunohistochemical analysis revealed the presence of a gut-brain peptide, neuromedin U (NMU), in the suprachiasmatic nucleus (SCN), which is the site of the master circadian oscillator. The expression of NMU mRNA exhibited a circadian rhythm, with the peak expression in the SCN occurring at CT4-8h. The two NMU-binding receptors (NMU-R1 and NMU-R2) were also expressed in the SCN, but their phase angles were different. Intracerebroventricular injection (ICV) of NMU induced the expression of Fos protein in the SCN cells and caused a phase-dependent phase shift of the circadian locomotor activity rhythm. The magnitude of the phase shift was dose dependent. This NMU-induced phase shift was of the nonphotic type. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed increases in the expression in the SCN of immediate early genes, such as c-fos, NGFI-A, NGFI-B, and JunB. Furthermore, ICV injection of NMU increased the expression of Per1, but not Per2, in the SCN. These results indicate that NMU may play some important role in the circadian oscillator by exerting an autocrine or paracrine action in the SCN.
Nakahara
Keiko
K
Department of Veterinary Physiology, Faculty of Agriculture, Miyazaki University, Miyazaki 889-2192, Japan.
Hanada
Reiko
R
Murakami
Noboru
N
Teranishi
Hitoshi
H
Ohgusu
Hideko
H
Fukushima
Nobuhiro
N
Moriyama
Maiko
M
Ida
Takanori
T
Kangawa
Kenji
K
Kojima
Masayasu
M
D000818:Animals; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D015870:Gene Expression; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D014157:Transcription Factors
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D017981:Receptors, Neurotransmitter; D014157:Transcription Factors; C082444:neuromedin U receptor; C056900:neuromedin U