Neuromedin U

Overview: Neuromedin U receptors (provisional nomenclature) are activated by the endogenous 25 amino-acid peptide neuromedin U (NMU), a peptide originally isolated from pig spinal cord (Minamino et al., 1985). In humans, NMU appears to be the sole product of a precursor (ENSG00000109255) showing a broad tissue distribution, but which is expressed at highest levels in the upper gastrointestinal tract, CNS, bone marrow and fetal liver. Much shorter versions of NMU are found in some species, but not human, and are derived at least in some instances from the proteolytic cleavage of the longer NMU. Despite species differences in NMU structure, the C-terminal region (particularly the C-terminal pentapeptide) is highly conserved and contains biological activity. Neuromedin S (NMS) has also been identified as an endogenous agonist (Mori et al., 2005). NMS is a 36 amino-acid product of a precursor protein derived from a single gene (ENSG00000204640) and contains an amidated C-terminal heptapeptide identical to NMU. NMS appears to activate NMU receptors with equivalent potency to NMU.

Nomenclature	NMU1	NMU2
Other names	GPR66, FM3, SNORF62 (Fujii et al., 2000; Hedrick et al., 2000; Hosoya et al., 2000; Howard et al., 2000; Kojima et al., 2000; Raddatz et al., 2000; Szekeres et al., 2000)	FM4, TGR1, SNORF72 (Hosoya et al., 2000; Howard et al., 2000; Raddatz et al., 2000; Shan et al., 2000)
Ensembl ID	ENSG00000171596	ENSG00000132911
Principal transduction	Gq/11 (Hedrick et al., 2000; Brighton et al., 2004a)	Gq/11 (Hosoya et al., 2000; Brighton et al., 2004a)
Antagonists	–	R-PSOP (Liu et al., 2009)

NMU1 and NMU2 couple predominantly to G_q/11 although there is evidence of coupling to G_i/o (see Hosoya et al., 2000; Brighton et al., 2004a; Hsu and Luo, 2007). NMU1 and NMU2 can be labelled with [¹²⁵I]-NMU and [¹²⁵I]-NMS (of various species, e.g. Meng et al., 2008), BODIPY® TMR-NMU or Cy3B-NMU-8 (Brighton et al., 2004a).

Glossary

Abbreviations:

NMS

neuromedin S

NMU

neuromedin U

R-PSOP

(R)-5′-(phenylaminocarbonylamino)spiro[1-azabicyclo[2.2.2.]octane-3,2′(3′H)-furo[2,3-b]pyridine]

Further Reading

Brighton PJ, Szekeres PG, Willars GB (2004b). Neuromedin U and its receptors: structure, function, and physiological roles. Pharmacol Rev56: 231–248.

Budhiraja S, Chugh A (2009). Neuromedin U: physiology, pharmacology and therapeutic potential. Fundam Clin Pharmacol23: 149–157.

Mitchell J, Maguire J, Davenport A (2009). Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin S. Br J Pharmacol158: 87–103.

Novak CM (2009). Neuromedin S and U. Endocrinology150: 2985–2987.