Neuromedin U

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Neuromedin U
Identifiers
SymbolNMU
Chr. 4 q12
Search for
StructuresSwiss-model
DomainsInterPro

Neuromedin U (NmU or NMU) is a neuropeptide found in the brain of humans and other mammals, which has a number of diverse functions including contraction of smooth muscle, regulation of blood pressure, pain perception, appetite, bone growth, and hormone release. It was first isolated from the spinal cord in 1985, and named after its ability to cause smooth muscle contraction in the uterus.[1][2][3][4][5][6][7][8]

Structure

Neuromedin U is a highly conserved neuropeptide present in many species, existing as multiple

amidated
at the C-terminus, and all isoforms have identical C-terminal heptapeptides.

The sequence of neuromedin U-23 in rats is: YKVNEYQGPVAPSGGFFLFRPRN-(NH2).[1]

Function

The activation of NmU receptors leads to intracellular

phosphoinositide (or PI) signaling, and the inhibition of cAMP production[10]

NmU will contract smooth muscle only in a tissue- and species-specific manner. Intracerebroventricular (or i.c.v) administration of the neuropeptide mediates stress response and increases both the arterial pressure and heart rate.

preganglionic neurons
, thus controlling the activity.

Regulation

Neuromedin U is mediated by two receptors, peripheral NmUR1 and central nervous system NmUR2. Both receptors are examples of Class A G-protein coupled receptors (or GPCRs) with a distinct distributional pattern. NmUR1 is expressed predominantly in the peripheral nervous system, with highest levels in the gastrointestinal tract, whereas NmUR2 is mostly found in the central nervous system, with greatest expression in the hypothalamus, medulla, and spinal cord.

The discovery of set distribution patterns has begun to allow assignation of specific roles of the two receptor subtypes within the body. What is known for certain is that recombinant NmU receptors will increase the internal calcium concentration, signaling via the MAPK/ERK pathway[11]

Role in disease

Cancer

Its role in cancer is not yet fully understood, though NmU and its receptor NMUR2 have been shown to be over-expressed in human pancreatic cancers compared to normal cells. Studies also showed NmU serum levels decreased after the tumors were removed, as NmU and its receptor are localized predominantly in cancer cells. Although NmU exerts no effect on cancer cell

paracrine loop regulating cell migration.[10]

Pain perception and stress response

The effect of NmU on stress and pain perception pathways has been demonstrated using mice. In contrast to NmU peptide-deficient mice, NmUR2

neurons
, a mechanism by which NmU stimulates pain, did not occur in NmUR2 KO mice. Both NmUR2 expression and NmU-23 binding sites are highly localized to the outer layers of the spinal dorsal horn, and administration of NmU via intracerebroventricular (ICV) injections usually increases pain sensitivity in rats and mice.

The expression of NmUR2 in the

genes in hypothalamic areas associated with stress, as well as stress-related behaviours that can be blocked by CRH antagonist
(this is absent from CRH knockout mice).

Certain stress responses are abolished in NmU knockout mice. These results suggest that NmU significantly modulates nociceptive sensory transmission.[9]

See also

References

  1. ^
    S2CID 884735
    .
  2. S2CID 23617159
    .
  3. PMID 17706946
    .
  4. PMID 17726140
    .
  5. S2CID 25260405
    .
  6. S2CID 33931881
    .
  7. S2CID 38382442
    .
  8. PMID 18987052
    .
  9. ^
    PMID 17030627
    .
  10. ^
    PMID 19118941
    .
  11. ^
    S2CID 25349752
    .

External links
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