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NmU involved in smooth muscle contraction, blood pressure, pain perception, appetite, and bone growth

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Bone remodeling, the function affected in osteoporosis, the most common of bone diseases, comprises two phases: bone formation by matrix-producing osteoblasts and bone resorption by osteoclasts. The demonstration that the anorexigenic hormone leptin inhibits bone formation through a hypothalamic relay suggests that other molecules that affect energy metabolism in the hypothalamus could also modulate bone mass. Neuromedin U (NMU) is an anorexigenic neuropeptide that acts independently of leptin through poorly defined mechanisms. Here we show that Nmu-deficient (Nmu?/?) mice have high bone mass owing to an increase in bone formation; this is more prominent in male mice than female mice. Physiological and cell-based assays indicate that NMU acts in the central nervous system, rather than directly on bone cells, to regulate bone remodeling. Notably, leptin- or sympathetic nervous system–mediated inhibition of bone formation was abolished in Nmu?/? mice, which show an altered bone expression of molecular clock genes (mediators of the inhibition of bone formation by leptin). Moreover, treatment of wild-type mice with a natural agonist for the NMU receptor decreased bone mass. Collectively, these results suggest that NMU may be the first central mediator of leptin-dependent regulation of bone mass identified to date. Given the existence of inhibitors and activators of NMU action, our results may influence the treatment of diseases involving low bone mass, such as osteoporosis.

 

NMU receptor type-1 (NMU1R) NMU receptor type-2 (NMU2R)
FM-3/GPR66 FM-4/TGR-1
Peripheral tissues CNS: PVN & SCN
NMU = NMS NMS > NMU

 
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Neuromedin U Neuromedin S
Brain-gut neuropeptide Neuro & Immunopeptide
Suppression of feeding Circadian rhythm regulation in the SCN
Regulation of energy homeostasis Immune response in the spleen
Elevation of arterial blood pressures and control of local blood flow Spermatogenesis in the testis
 
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Sato S, Hanada R, Kimura A, et al. Central control of bone remodeling by neuromedin U. Nat Med. 2007;13(10):1234-40.

Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which was isolated first from porcine spinal cord and later from other species. It is widely distributed in the gut and central nervous system. Peripheral activities of NMU include stimulation of smooth muscle, increase of blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. An NMU receptor has not been molecularly identified. Here we show that the previously described orphan G-protein-coupled receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues whereas FM-4, designated NMU2R, is expressed in specific regions of the brain. NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting. Intracerebroventricular administration of NMU markedly suppresses food intake in rats. These findings provide a molecular basis for the biochemical activities of NMU and may indicate that NMU is involved in the central control of feeding.

This publication used a Neuromedin U peptide, as well as 83 other peptides, from Phoenix Pharmaceuticals.
Howard AD, Wang R, Pong SS, et al. Identification of receptors for neuromedin U and its role in feeding. Nature. 2000;406(6791):70-4.

The discovery of neuropeptides has resulted in an increased understanding of novel regulatory mechanisms of certain physiological phenomena. Here we identify a novel neuropeptide of 36 amino-acid residues in rat brain as an endogenous ligand for the orphan G protein-coupled receptor FM-4/TGR-1, which was identified to date as the neuromedin U (NMU) receptor, and designate this peptide ‘neuromedin S (NMS)' because it is specifically expressed in the suprachiasmatic nuclei (SCN) of the hypothalamus. NMS shares a C-terminal core structure with NMU. The NMS precursor contains another novel peptide. NMS mRNA is highly expressed in the central nervous system, spleen and testis. In rat brain, NMS expression is restricted to the core of the SCN and has a diurnal peak under light/dark cycling, but remains stable under constant darkness. Intracerebroventricular administration of NMS in rats activates SCN neurons and induces nonphotic type phase shifts in the circadian rhythm of locomotor activity. These findings suggest that NMS in the SCN is implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.

Mori K, Miyazato M, Ida T, et al. Identification of neuromedin S and its possible role in the mammalian circadian oscillator system. The EMBO Journal. 2005;24(2):325-335. doi:10.1038/sj.emboj.7600526.


Related Products

Catalog# Product Standard Size Price
046-65 Neuromedin U-23 (Mouse) 100 µg $194
046-42 Neuromedin U-25 (Human) 200 µg $163
045-96 prepro-Neuromedin U (104-136) (Human) 100 µg $214
H-045-96 prepro-Neuromedin U (104-136) (Human) - Antibody 100 µl $459
B-045-96 prepro-Neuromedin U (104-136) (Human) - Biotin Labeled 10 µg $306
B-G-045-96 prepro-Neuromedin U (104-136) (Human) - Biotin Labeled Purified IgG 100 µl $505
FC3-G-045-96 prepro-Neuromedin U (104-136) (Human) - Cy3 Labeled Purified IgG 100 µl $607
FG-045-96A prepro-Neuromedin U (104-136) (Human) - FAM Labeled 1 nmol $306
FG-G-045-96A prepro-Neuromedin U (104-136) (Human) - FAM Labeled Purified IgG 100 µl $505
FG-G-045-96B prepro-Neuromedin U (104-136) (Human) - FITC Labeled Purified IgG 100 µl $505
T-045-96 prepro-Neuromedin U (104-136) (Human) - I-125 Labeled 10 µCi $723
T-G-045-96 prepro-Neuromedin U (104-136) (Human) - I-125 Labeled Purified IgG 10 µCi $723
G-045-96 prepro-Neuromedin U (104-136) (Human) - Purified IgG Antibody 200 µg $459
RK-045-96 prepro-Neuromedin U (104-136) (Human) - RIA Kit 125 tubes $588
FR-045-96 prepro-Neuromedin U (104-136) (Human) - Rhodamine Labeled 1 nmol $357
046-76 prepro-Neuromedin U (104-139) (Human) 100 µg $163
046-54 prepro-Neuromedin U (106-141) (Rat, Mouse) 100 µg $194
046-41 Neuromedin U (Rat) 200 µg $61
H-046-41 Neuromedin U (Rat) - Antibody 50 µl $459
B-G-046-41 Neuromedin U (Rat) - Biotin Labeled Purified IgG 100 µl $459
DBK-046-41 Neuromedin U (Rat) - Dot Blot Kit 5 blots $612
FG-046-41A Neuromedin U (Rat) - FAM Labeled 1 nmol $408
FG-G-046-41A Neuromedin U (Rat) - FAM Labeled Purified IgG 100 µl $459
T-046-41 Neuromedin U (Rat) - I-125 Labeled 10 µCi $723
T-G-046-41 Neuromedin U (Rat) - I-125 Labeled Purified IgG 10 µCi $723
G-046-41 Neuromedin U (Rat) - Purified IgG Antibody 200 µg $459
RK-046-41 Neuromedin U (Rat) - RIA Kit 125 tubes $671
FR-046-41 Neuromedin U (Rat) - Rhodamine Labeled 1 nmol $408
FR-G-046-41 Neuromedin U (Rat) - Rhodamine Labeled Purified IgG 100 µl $459
WBK-046-41 Neuromedin U (Rat) - Western Blot Kit 1 kit $624

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