Identification of neuromedin S and its possible role in the mammalian circadian oscillator system

Mori, Koichi; Miyazato, Minoru; Ida, Takanori; Murakami, Noboru; Serino, Ryota; Ueta, Yoichi; Kojima, Masayasu; Kangawa, Kenji

doi:10.1038/sj.emboj.7600526

Cited by 174 publications

(205 citation statements)

References 54 publications

Supporting

Mentioning

195

Contrasting

Order By: Relevance

“…Interestingly, a novel 33-residue peptide derived from the NMU proprotein has recently been identified and shows potent prolactin-releasing activity when administered i.c.v. (Williams et al 2001, Mori et al 2005. In the present study, the interaction of nutritional status and leptin with NMU gene expression in the pars tuberalis is clearly evidenced.…”

Section: Discussionsupporting

confidence: 55%

“…The NMU probe used in the present study has a portion of overlap with the known gene sequence of neuromedin S (NMS) and the possibility exists that some of the signal located in the present study corresponds to NMS gene expression. However, this is unlikely as NMS is almost exclusively localised to the SCN and its occurrence in the pars tuberalis has not been reported despite sections containing the closely neighbouring arcuate nuclei being observed (Mori et al 2005). …”

Section: Localisation Of Nmu and Ob-rb Gene Expressionmentioning

confidence: 98%

See 1 more Smart Citation

Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis

Nogueiras¹,

Tovar²,

Mitchell³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

Central neuromedin U (NMU) functions in energy balance, the hypothalamic-pituitary-adrenal axis, LH release and circadian rhythmicity. In rats, high levels of NMU occur in the hypothalamic suprachiasmatic nuclei and the pars tuberalis of the pituitary. NMU expression in the pars tuberalis appears to be downregulated in the Zucker fatty (fa/fa) rat, lacking functional leptin receptors. In contrast, in the dorsomedial (DMH) nuclei of the mouse, NMU expression is higher in the ob/ob mouse, lacking leptin, and is upregulated by fasting. However, leptin appears not to change NMU gene expression in either the mouse DMH or the rat pars tuberalis. Thus, the present study aims to better identify factors influencing central NMU expression in the rat pars tuberalis. SpragueDawley rats were fasted and/or challenged with intracerebroventricular leptin or ghrelin and gene expression was measured using real-time reverse transcriptase-PCR and quantitative in situ hybridisation with riboprobes specific for NMU and NMU receptor (NMU-R2). NMU expression in the rat pars tuberalis was elevated by fasting. Ghrelin administration had no effect on the level of NMU expression, but leptin was found to diminish the expression in a concentration-and time-dependent manner. NMU-R2 expression was unchanged in any of the groups measured. These results suggest that NMU expression in rat pars tuberalis is upregulated in states of negative energy balance, and this may be mediated indirectly by changes in leptin levels. These results demonstrate a link between energy balance and NMU expression in the pars tuberalis of the pituitary.

show abstract

Section: Discussionsupporting

confidence: 55%

Section: Localisation Of Nmu and Ob-rb Gene Expressionmentioning

confidence: 98%

Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis

Nogueiras¹,

Tovar²,

Mitchell³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Mammalian NMU and NMS share the C-terminal heptapeptide-amide 1a (H-Phe 0 -Leu 1 -Phe 2 -Arg 3 -Pro 4 -Arg 5 -Asn 6 -NH 2 , Figure 1A), which activates both receptors. 1,2 In 1995, Hashimoto et al reported that N-terminal succinylated 1a, which was synthesized as an aminopeptidase-resistant derivative, showed potent contractile activity toward chicken crop smooth muscle expressing avian NMU receptors. 10 Recently, we performed a structure−activity relationship (SAR) study of heptapeptide 1a to develop receptor-selective agonists using cultured cells expressing human NMU receptors.…”

mentioning

confidence: 99%

Discovery of Potent Hexapeptide Agonists to Human Neuromedin U Receptor 1 and Identification of Their Serum Metabolites

Takayama

Mori

Sohma

et al. 2015

ACS Med. Chem. Lett.

Self Cite

View full text Add to dashboard Cite

Neuromedin U (NMU) and S (NMS) display various physiological activities, including an anorexigenic effect, and share a common C-terminal heptapeptide-amide sequence that is necessary to activate two NMU receptors (NMUR1 and NMUR2). On the basis of this knowledge, we recently developed hexapeptide agonists 2 and 3, which are highly selective to human NMUR1 and NMUR2, respectively. However, the agonists are still less potent than the endogenous ligand, hNMU. Therefore, we performed an additional structure−activity relationship study, which led to the identification of the more potent hexapeptide 5d that exhibits similar NMUR1-agonistic activity as compared to hNMU. Additionally, we studied the stability of synthesized agonists, including 5d, in rat serum, and identified two major biodegradation sites: Phe 2 -Arg 3 and Arg 5 -Asn 6 . The latter was more predominantly cleaved than the former. Moreover, substitution with 4-fluorophenylalanine, as in 5d, enhanced the metabolic stability at Phe 2 -Arg 3 . These results provide important information to guide the development of practical hNMU agonists.

show abstract

“…In contrast, they strongly suggest the involvement of NMU in the physiological regulation of the biological activity of immature rat adrenocortical cells. It has been suggested that NMU exerts its biological effects mainly via autocrine-paracrine mechanisms (53). However, the expression of NMU gene was not detected in the rat adrenals (33).…”

Section: Discussionmentioning

confidence: 97%

Effects of neuromedin-U on immature rat adrenocortical cells: In vitro and in vivo studies

Ziółkowska¹,

Macchi²,

Trejter³

et al. 2008

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Neuromedin U (NMU) is a brain-gut peptide, that in the peripheral organs and tissues acts via a G protein-coupled receptor, called NMUR1. Reverse transcription-polymerase chain reaction showed the expression of NMUR1 mRNA in either cortex and medulla or dispersed zona glomerulosa and zona fasciculata-reticularis cells of the immature rat adrenals. Accordingly, immunocytochemistry demonstrated the presence of NMUR1-like immunoreactivity in the cortex and medulla of immature adrenals. NMU8 administration to immature rats was found to raise aldosterone, but not corticosterone, plasma concentration, without altering adrenal growth. Conversely, the exposure to NMU8 markedly enhanced the proliferative activity of immature rat inner adrenocortical cells in primary in vitro culture, without significantly affecting their corticosterone secretion. Collectively, our findings suggest that adrenals of immature rats may be a target for circulating NMU. However, the physiological significance and relevance of the adrenal effects of NMU remain to be ascertained.

show abstract

Identification of neuromedin S and its possible role in the mammalian circadian oscillator system

Cited by 174 publications

References 54 publications

Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis

Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis

Discovery of Potent Hexapeptide Agonists to Human Neuromedin U Receptor 1 and Identification of Their Serum Metabolites

Effects of neuromedin-U on immature rat adrenocortical cells: In vitro and in vivo studies

Contact Info

Product

Resources

About