Localization of 7B2, Neuromedin B, and Neuromedin U in Specific Cell Types of Rat, Mouse, and Human Pituitary, in Rat Hypothalamus, and in 30 Human Pituitary and Extrapituitary Tumors

Steel, Jennifer H.; Noorden, Susan Van; Ballesta, José Antonio Camacho; Gibson, Susan E.; Ghatei, Mohammed A.; Burrin, Jacky M.; Leonhardt, U.; Domin, Jan; Bloom, Stephen R.; Polak, Julia M.

doi:10.1210/endo-122-1-270

Cited by 118 publications

(93 citation statements)

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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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“…Estudos imunocitoquími-cos revelaram co-localização de neuromedina B e TSH em adeno-hipófises de ratos, sugerindo que ela seja sintetizada pelos tireotrofos murinos (32,37).…”

Section: Neuromedina B E Grp Na Hipófiseunclassified

“…Houben et al (24) observaram aumento nos níveis de RNA mensageiro para neuromedina B após tratamento de cultura de células re-agregadas de hipófise com estrogênio. O conteúdo de neuromedina B na adeno-hipófise muda de acordo com a função tireóidea, estando aumentado no hipertireoidismo e diminuído em animais tireoidectomizados (37,38), indicando regulação de sua síntese pelos hormônios tireóideos (38).…”

Section: Neuromedina B E Grp Na Hipófiseunclassified

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Peptídeos bombesina-símiles: novos reguladores da secreção adeno-hipofisária

Ortiga-Carvalho

Pazos‐Moura

2000

Arq Bras Endocrinol Metab

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A neuromedina B (NB) e o peptídeo liberador de gastrina são peptídeos bombesina-símiles encontrados em mamíferos, inclusive em seres humanos. Ambos inibem a secreção hipofisária de tireotrofina (TSH); entretanto, somente a NB tem importância fisiológica demonstrada. A NB é produzida em abundância em tireotrofos e parece inibir a secreção de TSH por via autócrina, uma vez que o bloqueio do peptídeo endógeno causa aumento na liberação do TSH, tanto in vivo quanto in vitro. A NB é positivamente regulada pelos hormônios tireóideos (HT). Os HT aumentam o conteúdo de neuromedina B e do seu RNAm em adeno-hipófises de ratos hipotireóideos, poucas horas após sua administração, o que coincide com diminuição do TSH sérico. Isto nos levou a sugerir que a NB possa ser um intermediário protéico envolvido na inibição aguda da liberação de TSH induzida pelos HT. O TRH também altera rapidamente a expressão da NB. Quinze e 30 minutos após a administração do TRH em ratos normais já há diminuição do conteúdo hipofisário de NB e dos níveis do seu RNAm. No jejum e diabetes experimental, que se caracterizam por diminuição de HT séricos com níveis inadequadamente normais ou diminuídos de TSH, ocorre aumento do conteúdo de NB e de seu RNAm. O análogo de somatostatina, octreotide, também é capaz de aumentar o conteúdo de NB. Assim, a neuromedina B é um importante inibidor local da secreção de TSH, podendo ser uma via final comum de hormônios e neuro-hormônios que determinam variações na secreção de TSH. ABSTRACTNeuromedin B (NB) and gastrin-releasing peptide (GRP) are mammalian bombesin-like peptides. Both peptides have inhibitory effects on thyrotropin (TSH) secretion, however NB is the one that proved to be physiologically relevant. The administration of NB reduces serum TSH of eu-and hypothyroid rats, while the antiserum against NB, that blocks the endogenous peptide, increases TSH secretion. NB is abundantly produced in thyrotrophs and acts locally as a autocrine factor to inhibit TSH release since isolated pituitaries increase the release of TSH in the presence of the specific antiserum. Thyroid hormones (TH) up-regulate pituitary NB peptide and mRNA content. This is a rapid effect: in hypothyroid rats it is seen within a few hours after a single injection of TH, and coincides with TSH suppression. These results suggest that NB could be an intermediary factor in the acute suppressive effect of TH on TSH secretion. TRH also rapidly changes NB expression. In normal rats, 15 to 30 minutes after TRH administration the pituitary NB peptide and mRNA content are already decreased. In experimental fasting and diabetes mellitus, which are characterized by inappropriately normal or decreased serum TSH, both the NB peptide and its mRNA pituitary content are increased. Octreotide, a somatostatin analog, also is able to increase pituitary neu-

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“…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: 95%

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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Localization of 7B2, Neuromedin B, and Neuromedin U in Specific Cell Types of Rat, Mouse, and Human Pituitary, in Rat Hypothalamus, and in 30 Human Pituitary and Extrapituitary Tumors

Cited by 118 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

Peptídeos bombesina-símiles: novos reguladores da secreção adeno-hipofisária

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

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