Expression of neuromedins S and U and their receptors in the hypothalamus and endocrine glands of the rat

Ruciński, Marcin; Ziółkowska, Agnieszka; Neri, Giuliano; Trejter, Marcin; Zemleduch, Tomasz; Tyczewska, Marianna; Nussdorfer, Gastone G.; Malendowicz, Ludwik K.

doi:10.3892/ijmm.20.2.255

Cited by 18 publications

(32 citation statements)

References 45 publications

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“…Our present RT-PCR and ICC studies clearly demonstrate the expression of NMUR1 as mRNA and protein in the cortex of immature rat adrenals, thereby confirming earlier findings obtained in adult animals (9,(27)(28)(29)33,34). Moreover, the detection of NMUR1 mRNA in dispersed zona glomerulosa and zona fasciculata-reticularis cells rules out the possibility that the expression was due to the presence in the specimens assayed of the non-parenchymal components of the gland (connective tissue and capillaries).…”

Section: Discussionsupporting

confidence: 77%

“…However, the expression of NMU gene was not detected in the rat adrenals (33). Phoenix Pharmaceuticals has recently made available kits for NMU assay, that showed that this peptide may attain in human plasma concentrations of ~10 -8 M (30 pg/ml) (33). Hence, it is reasonable to conceive that NMU may activate adrenocortical NMUR1 acting as a true circulating hormone.…”

Section: Discussionmentioning

confidence: 99%

“…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). Phoenix Pharmaceuticals has recently made available kits for NMU assay, that showed that this peptide may attain in human plasma concentrations of ~10 -8 M (30 pg/ml) (33).…”

Section: Discussionmentioning

confidence: 99%

“…NPY, cholecystokinin, galanin, leptin, orexins, beacon and NPW) (11)(12)(13)(14)(15)(16)(17), also NMU appears to regulate the hypothalamic-pituitary-adrenal (HPA) axis. The expression of NMU and NMUR 2 was found in the hypothalamus and anterior pituitary (10,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), while in the adrenal glands only the expression of NMUR1 was detected (9,(27)(28)(29)33,34). NMU has been shown to enhance c-fos expression in the hypothalamic paraventricular nucleus (1,2,30,35), to increase CRH and vasopressin output from rat hypothalamic explants, and to stimulate ACTH and corticosterone secretion in the rat (2,4,5,(36)(37)(38).…”

Section: Introductionmentioning

confidence: 98%

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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

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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.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

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

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“…Semiquantitative real-time PCR was performed as previously detailed (22)(23)(24) in a Roche LightCycler 2.0 with software version 4.0, using the following primers: i) StAR sense (684-703), 5'-CCTGAGCAAAGCGG TGTCAT-3' and antisense (850-870), 5'-GCAAGTGGCTGG CGAACTCTA-3' (amplifon, 187 bp; accession number, NM-03155); and ii) HPRT (hypoxanthine guanine phosphoribosyl transferase 1) sense (391-412), 5'-CAGTCAACGGGGG ACATAAAAG-3' and antisense (515-536), 5'-ATTTTGG GGCTGTACTGCTTGA-3' (amplicon, 146 bp; accession number, NM-01258). The PCR program was: denaturation step at 95˚C for 10 min, 45 cycles of three amplification steps (95˚C for 10 sec, annealing at 58˚C for 5 sec, and extension at 72˚C for 10 sec), and melting curve at 60-90˚C with a heating rate of 0.1˚C/sec.…”

Section: Reverse Transcription (Rt)-polymerase Chain Reaction (Pcr)mentioning

confidence: 99%

Steroidogenic acute regulatory protein gene expression, steroid-hormone secretion and proliferative activity of adrenocortical cells in the presence of proteasome inhibitors: In vivo studies on the regenerating rat adrenal cortex

Ruciński¹,

Tortorella²,

Ziółkowska³

et al. 2008

Int J Mol Med

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Abstract.Previous studies have shown that proteasome inhibitors promote the accumulation of steroidogenic acute regulatory protein (StAR) in cultured rat adrenocortical cells. Unexpectedly, this response was associated with a moderate lowering in the corticosterone secretion and proliferation rate of cultured cells. Hence, we studied the effects of proteasome inhibitors MG115 and MG132 on the secretion and proliferative activity of the regenerating adrenal cortex in rats 5 days after surgery. Animals were given two subcutaneous injections of 0.15 or 1.5 nmol/100 g of inhibitors 24 and 12 h before decapitation. Real-time PCR and Western blotting showed that StAR expression, both mRNA and protein, was markedly lower in regenerating adrenals than in the intact gland of sham-operated rats. Neither MG115 nor MG132 affected StAR expression in regenerating gland. Inhibitors induced a slight decrease in the plasma concentrations of aldosterone and corticosterone, but did not significantly alter metaphase index of the regenerating adrenal cortex. Our findings provide the first evidence that down-regulation of StAR occurs during the early stages of adrenal regeneration. Moreover, this suggests that the steroidogenic pathway is more sensitive to proteasome inhibitors than that regulating proliferative activity of regenerating adrenal cortex in the rat.

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Synthesis and evaluation of novel lipidated neuromedin U analogs with increased stability and effects on food intake

et al. 2014

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Neuromedin U (NMU) is a 25 amino acid peptide expressed and secreted in the brain and gastrointestinal tract. Data have shown that peripheral administration of human NMU decreases food intake and body weight and improves glucose tolerance in mice, suggesting that NMU receptors constitute a possible anti-diabetic and anti-obesity drug target. However, the clinical use of native NMU is hampered by a poor pharmacokinetic profile. In the current study, we report in vitro and in vivo data from a series of novel lipidated NMU analogs. In vitro plasma stability studies of native NMU were performed to investigate the proteolytic stability and cleavage sites using LC-MS. Native NMU was found to be rapidly cleaved at the C-terminus between Arg(24) and Asn(25) , followed by cleavage between Arg(16) and Gly(17) . Lipidated NMU analogs were generated using solid-phase peptide synthesis, and in vitro potency was investigated using a human embryonic kidney 293-based inositol phosphate accumulation assay. All lipidated analogs had preserved in vitro activity on both NMU receptors with potency improving as the lipidation site was moved away from the receptor-interacting C-terminal octapeptide segment. In vivo efficacy was assessed in lean mice as reduction in food intake after acute subcutaneous administration of 1, 0.3, 0.1, and 0.03 µmol/kg. These lipidated NMU analogs prolonged the anorectic effect of NMU in a dose-dependent manner. This was likely an effect of improved pharmacokinetic properties because of improved vitro plasma stability. Accordingly, the data demonstrate that lipidated NMU analogs may represent drug candidates for the treatment of obesity.

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Expression of neuromedins S and U and their receptors in the hypothalamus and endocrine glands of the rat

Cited by 18 publications

References 45 publications

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

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

Steroidogenic acute regulatory protein gene expression, steroid-hormone secretion and proliferative activity of adrenocortical cells in the presence of proteasome inhibitors: In vivo studies on the regenerating rat adrenal cortex

Synthesis and evaluation of novel lipidated neuromedin U analogs with increased stability and effects on food intake

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