Cloning and characterization of the cDNA encoding the human neuromedin U (NmU) precursor: NmU expression in the human gastrointestinal tract

Austin, Carol; Lo, Gar; Nandha, Kiran A.; Meleagros, L; Bloom, Steve

doi:10.1677/jme.0.0140157

Cited by 73 publications

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“…Considering these results together, the reported action of neuromedin U on uterine tissue would appear to be primarily mediated by TGR-1. It has been reported that both neuromedin U mRNA and neuromedin U-like immunoreactivity are abundantly detected in the human and rat pituitary gland (17,24,25). We detected the highest level of neuromedin U mRNA expression in the rat pituitary gland (10).…”

Section: Discussionsupporting

confidence: 46%

Identification and Functional Characterization of a Novel Subtype of Neuromedin U Receptor

Hashimoto

Moriya

Kawamata

et al. 2000

Journal of Biological Chemistry

113

110

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Neuromedin U is a bioactive peptide isolated originally from the porcine spinal cord. We recently identified neuromedin U as the cognate ligand for the orphan G protein-coupled receptor FM-3. In this study, we isolated cDNA coding for a novel G protein-coupled receptor, TGR-1, which was highly homologous with FM-3. We found that neuromedin U specifically and clearly elevated the extracellular acidification rates, arachidonic acid metabolite release, and intracellular Ca 2؉ mobilization in Chinese hamster ovary cells expressing TGR-1. Radiolabeled neuromedin U specifically bound with high affinity to membrane fractions prepared from these cells. These results show that TGR-1, like FM-3, is a specific and functional receptor for neuromedin U. We analyzed TGR-1 mRNA tissue distribution in rats using quantitative reverse transcription-polymerase chain reaction and found it to considerably differ from that of FM-3 mRNA. TGR-1 mRNA was primarily expressed in the uterus, suggesting that TGR-1 mediates the contractile activity of neuromedin U in this tissue. The identification of specific and functional receptor subtypes for neuromedin U will facilitate the study of their physiological roles and the search for their specific agonists and antagonists.The bioactive peptides neuromedin U-8 and U-25 were originally isolated from the porcine spinal cord based on their powerful contractile activity in the uterine smooth muscle of rats (1, 2). Since then, neuromedin U has been found to show various biological activities including the elevation of blood pressure and the induction of adrenocorticotropin and corticosterone release in vivo in rats (1, 3-6). Applying our previously described strategy to identify endogenous ligands for orphan G protein-coupled receptors (GPCRs) 1 (7-9), we recently succeeded in demonstrating that the orphan GPCR, FM-3, a homologue of the neurotensin (NT) and growth hormone secretagogue receptors, is a specific and functional receptor for neuromedin U (10). When FM-3 was expressed in Chinese hamster ovary (CHO) cells, neuromedin U induced specific and clear elevation of extracellular acidification rates, arachidonic acid metabolite (AA) release, and intracellular Ca 2ϩ mobilization. Radiolabeled neuromedin U specifically bound with high affinity to membrane fractions prepared from these cells. Our analyses for FM-3 mRNA expression levels using quantitative reverse transcription-polymerase chain reaction (RT-PCR) indicated that FM-3 mRNA was expressed highly in the small intestine and lung of rats, but only very low levels were detected in the uterus. Nonetheless neuromedin U has reportedly shown very strong contractile activity (1, 2), and numerous binding sites have been detected in rat uterine tissue (11, 12). We considered that this discrepancy might be due to the existence of an unknown receptor subtype for neuromedin U in the rat uterus. We therefore searched for another neuromedin U receptor subtype in addition to FM-3.In this paper, we report on the isolation of human and rat cDNA encoding a n...

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Section: Discussionsupporting

confidence: 46%

Identification and Functional Characterization of a Novel Subtype of Neuromedin U Receptor

Hashimoto

Moriya

Kawamata

et al. 2000

Journal of Biological Chemistry

113

110

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“…In human tissue, NmU mRNA is found in the intestine, stomach, pituitary gland and several brain regions, including hypothalamus, locus coeruleus, thalamus, medulla and substantia nigra; it is also found in lymphoid cells (Sumi et al 1987, Austin et al 1995, Raddatz et al 2000. A similar expression pattern is observed in rat (Domin et al 1987, Fujii et al 2000 and mouse (Funes et al 2002).…”

Section: Introductionmentioning

confidence: 59%

“…Two active peptides were identified in this work: an amidated 25-amino-acid peptide that is generated by enzymatic cleavage at the C-terminal region of a 174-amino-acid precursor (Lo et al 1992) and an 8-amino-acid cleavage product of NmU-25 (NmU-8) (Minamino et al 1985b), both of which possess smooth muscle contractile activity (Minamino et al 1985a,b). NmU cDNAs from dog, rabbit, frog, rat and human have been cloned (Domin et al 1989, Kage et al 1991, O'Harte et al 1991, Lo et al 1992, Austin et al 1995 and demonstrate a strong amino-acid sequence homology. In particular, it has been shown that the C-terminal heptapeptide core of NmU (FLFRPRN-NH 2 ) constitutes a conserved domain that is sufficient for biologic activity (Hashimoto et al 1991).…”

Section: Introductionmentioning

confidence: 99%

Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice

Kowalski¹,

Spar²,

Markowitz³

et al. 2005

Journal of Endocrinology

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Recent work has shown that neuromedin U (NmU), a peptide initially identified as a smooth muscle contractor, may play a role in regulating food intake and energy homeostasis. To further evaluate this putative function, we measured food intake, body weight, energy expenditure and glucose homeostasis in transgenic mice that ubiquitously overexpress murine proNmU. NmU transgenic mice were lighter and had less somatic and liver fat, were hypophagic, and had improved insulin sensitivity as judged by an intraperitoneal insulin tolerance test. Transgenic mice had higher levels of hypothalamic NPY, POMC and MCH mRNA. There was no difference in O 2 consumption between genotypes; however, NmU transgenic mice displayed a modest increase in respiratory quotient during food deprivation and refeeding. There were no behavioral disturbances in the NmU transgenic mice that could account for the results (e.g. changes in locomotor activity). When placed on a high-fat diet, transgenic mice remained lighter than wild-type mice and ate less, but gained weight at a rate similar to wild-type mice. Despite the increased weight gain with high-fat feeding, glucose tolerance was significantly improved in the transgenic mice. These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide.

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“…Neuromedin U (NMU) is a highly conserved brain-gut peptide that was first isolated from the porcine spinal cord (Minamino et al 1985) and later from the brain, spinal cord, and intestine of other species (Domin et al 1986, 1989, O'Harte et al 1991, Austin et al 1995. Thus far, the only known physiological role of NMU is contraction of smooth muscles in blood vessels, the uterus, and the gastrointestinal tract (Minamino et al 1985).…”

Section: Introductionmentioning

confidence: 99%

Comparison of feeding suppression by the anorexigenic hormones neuromedin U and neuromedin S in rats

Nakahara

Katayama

Maruyama³

et al. 2010

Journal of Endocrinology

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We compared the central mechanisms of feeding suppression by the anorexigenic hormones neuromedin U (NMU) and neuromedin S (NMS) in rats. I.c.v. injection of either NMU or NMS dose dependently decreased 3-h food intake during the first quarter of a dark period. Pretreatment involving i.c.v. injection of a specific anti-NMS IgG blocked the suppression of food intake induced by i.c.v.-and i.p.-injected leptin, but anti-NMU IgG elicited no blockade. Quantitative PCR analysis revealed that i.c.v. injection of NMU or NMS caused a dose-dependent increase in CRH and proopiomelanocortin mRNA expression in the paraventricular nucleus (PVN) and arcuate nucleus (Arc) respectively. In tissue cultures of the Arc, secretion of a-melanocyte-stimulating hormone was stimulated by NMU and NMS, with more potent stimulation by NMS. The time-course curves of the increase in neuronal firing rate in Arc slices in response to NMU and NMS showed almost the same pattern, with a peak 10-15 min after treatment, whereas the time-course curves for the PVN slices differed between NMU and NMS. These results suggest that NMS and NMU may share anorexigenic effects, depending on physiological conditions.

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Cloning and characterization of the cDNA encoding the human neuromedin U (NmU) precursor: NmU expression in the human gastrointestinal tract

Cited by 73 publications

References 0 publications

Identification and Functional Characterization of a Novel Subtype of Neuromedin U Receptor

Identification and Functional Characterization of a Novel Subtype of Neuromedin U Receptor

Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice

Comparison of feeding suppression by the anorexigenic hormones neuromedin U and neuromedin S in rats

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