The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Kenji Kangawa - One of the best experts on this subject based on the ideXlab platform.
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NeUromedin U sUppresses prolactin secretion via dopamine neUrons of the arcUate nUcleUs
Biochemical and Biophysical Research Communications, 2020Co-Authors: Keiko Nakahara, Kenji Kangawa, Masamitsu Nakazato, Kenji Mori, Mikiya Miyazato, Takuya Ensho, Keisuke Maruyama, Ryoko Uemura, Hideyuki Sakoda, Noboru MurakamiAbstract:Abstract NeUromedin U (NMU) has a precUrsor that contains one additional peptide consisting of 33 or 36 amino acid residUes. Recently, we identified this second peptide from rat brain and designated it NeUromedin U precUrsor-related peptide (NURP), showing it to stimUlate prolactin release from the pitUitary when injected via the intracerebroventricUlar (icv) roUte. Here, we examined whether NMU, like NURP, also stimUlates prolactin release. Unlike NURP, icv injection of NMU significantly decreased the secretion of prolactin from the pitUitary. This sUppression of prolactin release by NMU was observed in hyper-prolactin states sUch as lactation, stress, pseUdopregnancy, domperidone (dopamine antagonist) administration, and icv injection of NURP. ImmUnohistochemical analysis revealed that icv injection of NMU indUced cFos expression in dopaminergic neUrons of the arcUate nUcleUs, bUt not the sUbstantia nigra. Mice with doUble knockoUt of NMU and NeUromedin S (NMS), the latter also binding to NMU receptors, showed a significant increase of the plasma prolactin level after domperidone treatment relative to wild-type mice. These resUlts sUggest that NMU and NURP may play important reciprocal roles in physiological prolactin secretion.
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NeUromedin U precUrsor related peptide nUrp exerts NeUromedin U like sympathetic nerve action in the rat
Biochemical and Biophysical Research Communications, 2017Co-Authors: Takuya Ensho, Kenji Kangawa, Kenji Mori, Mikiya Miyazato, Keisuke Maruyama, Keiko Nakahara, Noboru MurakamiAbstract:Abstract It has been sUggested that novel peptide that is prodUced from the NeUromedin U (NMU) precUrsor may exist, as this precUrsor contains mUltiple consensUs seqUences for proteolytic processing. Recently, we identified two matUre novel peptides comprising 33 and 36 residUes in the rat brain, which were designated NeUromedin U precUrsor-related peptide (NURP) 33 and 36. In the present stUdy, we compared the roles of NURP33 and 36 with that of NMU, as neither activates the NMU receptors. ImmUnoreactivity for NMU and NURPs was widely present in the central nervoUs system and showed a similar distribUtion. IntracerebroventricUlar (icv) injection of NURP33 in rats increased locomotor activity, energy expenditUre, heart rate and back sUrface temperatUre (BS-T), similarly to NMU or NURP36. NMU treatment redUced food intake, bUt NURP33 did not. Pretreatment with the β3 blocker, SR59230A, and the cyclooxygenase blocker, indomethacin, inhibited the NURP33- or NMU-indUced increase of BS-T. In addition, icv injection of NURP33 or NMU increased the expression of mRNA for cyclooxygenase 2 in the hypothalamUs and for UncoUpling protein 1 in the brown adipose tissUe. These resUlts sUggest that althoUgh NURP33 and 36 do not activate the NMU receptors, they might exert NMU-like sympathetic nerve action in the brain.
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identification of NeUromedin U precUrsor related peptide and its possible role in the regUlation of prolactin release
Scientific Reports, 2017Co-Authors: Kenji Mori, Mikiya Miyazato, Keiko Nakahara, Noboru Murakami, Jun Hino, Mami Fudetani, Miwa Mori, Hiroyuki Kaiya, Kenji KangawaAbstract:The discovery of neUropeptides provides insights into the regUlation of physiological processes. The precUrsor for the neUropeptide NeUromedin U contains mUltiple consensUs seqUences for proteolytic processing, sUggesting that this precUrsor might generate additional peptides. We performed immUnoaffinity chromatography of rat brain extracts and conseqUently identified sUch a prodUct, which we designated NeUromedin U precUrsor-related peptide (NURP). In rat brain, NURP was present as two matUre peptides of 33 and 36 residUes. RadioimmUnoassays revealed NURP immUnoreactivity in the pitUitary, small intestine, and brain of rats, with the most intense reactivity in the pitUitary. IntracerebroventricUlar administration of NURP to both male and female rats robUstly increased plasma concentrations of prolactin bUt not of other anterior pitUitary hormones. In contrast, NURP failed to stimUlate prolactin release from dispersed anterior pitUitary cells. Pretreatment of rats with bromocriptine, a dopamine receptor agonist, blocked the prolactin-releasing activity of NURP. In rats pretreated with the antagonist sUlpiride, intracerebroventricUlar administration of NURP did not increase plasma prolactin concentrations more than administration of saline. These data sUggest that NURP indUces prolactin release by acting indirectly on the pitUitary; dopamine from the hypothalamUs, which inhibits prolactin release, may be involved in this activity of NURP.
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NeUromedin U is necessary for normal gastrointestinal motility and is regUlated by serotonin
Annals of the New York Academy of Sciences, 2010Co-Authors: Yoshiki Nakashima, Kenji Kangawa, Kenji Mori, Mikiya Miyazato, Takahiro Sato, Tomoko Takahashi, Yuki Nakamura, Jingo Kusukawa, Masayasu KojimaAbstract:NeUromedin U (NMU) was originally isolated from porcine spinal cord and shown to be distribUted in nUmeroUs tissUes, inclUding the gastrointestinal tract. However, little is known aboUt the role of NMU in the regUlation of gastrointestinal fUnctions. We established a radioimmUnoassay system that is exceptionally specific for moUse NMU and foUnd high NMU content in the gastrointestinal tract, particUlarly in the AUerbach's and Meissner's plexi, sUggesting a possible role of NMU in gastrointestinal motility. NMU promoted small intestinal transit, and NMU deficiency resUlted in lowered intestinal motility rate and diminished the effect of serotonin-indUced defecation and diarrhea. These resUlts indicate that NMU promotes intestinal transit and maintains intestinal homeostasis.
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NeUromedin U-like immUnoreactivity in rat intestine: regional distribUtion and immUnohistochemical stUdy.
Neuropeptides, 2004Co-Authors: M. Honzawa, Naoto Minamino, Kenji Kangawa, Tetsuji Sudoh, Hisayuki MatsuoAbstract:Abstract NeUromedin U-25 and its C-terminal octapeptide, NeUromedin U-8 are related peptides originally identified in porcine brain which elicit potent UterUs stimUlant activity. RadioimmUnoassay Using an antiserUm raised against porcine NeUromedin U-8, indicated that NeUromedin U-like immUnoreactivity in the rat was far more abUndant in the small intestine than the brain. NeUromedin U in the rat is a single, a 23 amino acid peptide (2, 17). Rat NeUromedin U has the same 7 residUes on its C-terminUs as porcine NeUromedin U, and the antiserUm against porcine NeUromedin U-8 is 100% crossreactive with rat NeUromedin U. ImmUnohistochemical analyses Using this antiserUm revealed that NeUromedin U-immUnoreactive strUctUres in rat intestine were confined to the enteric nervoUs system, implying that NeUromedin U may be involved in neUronal regUlation of gUt fUnction.
Noboru Murakami - One of the best experts on this subject based on the ideXlab platform.
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NeUromedin U sUppresses prolactin secretion via dopamine neUrons of the arcUate nUcleUs
Biochemical and Biophysical Research Communications, 2020Co-Authors: Keiko Nakahara, Kenji Kangawa, Masamitsu Nakazato, Kenji Mori, Mikiya Miyazato, Takuya Ensho, Keisuke Maruyama, Ryoko Uemura, Hideyuki Sakoda, Noboru MurakamiAbstract:Abstract NeUromedin U (NMU) has a precUrsor that contains one additional peptide consisting of 33 or 36 amino acid residUes. Recently, we identified this second peptide from rat brain and designated it NeUromedin U precUrsor-related peptide (NURP), showing it to stimUlate prolactin release from the pitUitary when injected via the intracerebroventricUlar (icv) roUte. Here, we examined whether NMU, like NURP, also stimUlates prolactin release. Unlike NURP, icv injection of NMU significantly decreased the secretion of prolactin from the pitUitary. This sUppression of prolactin release by NMU was observed in hyper-prolactin states sUch as lactation, stress, pseUdopregnancy, domperidone (dopamine antagonist) administration, and icv injection of NURP. ImmUnohistochemical analysis revealed that icv injection of NMU indUced cFos expression in dopaminergic neUrons of the arcUate nUcleUs, bUt not the sUbstantia nigra. Mice with doUble knockoUt of NMU and NeUromedin S (NMS), the latter also binding to NMU receptors, showed a significant increase of the plasma prolactin level after domperidone treatment relative to wild-type mice. These resUlts sUggest that NMU and NURP may play important reciprocal roles in physiological prolactin secretion.
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NeUromedin U precUrsor related peptide nUrp exerts NeUromedin U like sympathetic nerve action in the rat
Biochemical and Biophysical Research Communications, 2017Co-Authors: Takuya Ensho, Kenji Kangawa, Kenji Mori, Mikiya Miyazato, Keisuke Maruyama, Keiko Nakahara, Noboru MurakamiAbstract:Abstract It has been sUggested that novel peptide that is prodUced from the NeUromedin U (NMU) precUrsor may exist, as this precUrsor contains mUltiple consensUs seqUences for proteolytic processing. Recently, we identified two matUre novel peptides comprising 33 and 36 residUes in the rat brain, which were designated NeUromedin U precUrsor-related peptide (NURP) 33 and 36. In the present stUdy, we compared the roles of NURP33 and 36 with that of NMU, as neither activates the NMU receptors. ImmUnoreactivity for NMU and NURPs was widely present in the central nervoUs system and showed a similar distribUtion. IntracerebroventricUlar (icv) injection of NURP33 in rats increased locomotor activity, energy expenditUre, heart rate and back sUrface temperatUre (BS-T), similarly to NMU or NURP36. NMU treatment redUced food intake, bUt NURP33 did not. Pretreatment with the β3 blocker, SR59230A, and the cyclooxygenase blocker, indomethacin, inhibited the NURP33- or NMU-indUced increase of BS-T. In addition, icv injection of NURP33 or NMU increased the expression of mRNA for cyclooxygenase 2 in the hypothalamUs and for UncoUpling protein 1 in the brown adipose tissUe. These resUlts sUggest that althoUgh NURP33 and 36 do not activate the NMU receptors, they might exert NMU-like sympathetic nerve action in the brain.
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identification of NeUromedin U precUrsor related peptide and its possible role in the regUlation of prolactin release
Scientific Reports, 2017Co-Authors: Kenji Mori, Mikiya Miyazato, Keiko Nakahara, Noboru Murakami, Jun Hino, Mami Fudetani, Miwa Mori, Hiroyuki Kaiya, Kenji KangawaAbstract:The discovery of neUropeptides provides insights into the regUlation of physiological processes. The precUrsor for the neUropeptide NeUromedin U contains mUltiple consensUs seqUences for proteolytic processing, sUggesting that this precUrsor might generate additional peptides. We performed immUnoaffinity chromatography of rat brain extracts and conseqUently identified sUch a prodUct, which we designated NeUromedin U precUrsor-related peptide (NURP). In rat brain, NURP was present as two matUre peptides of 33 and 36 residUes. RadioimmUnoassays revealed NURP immUnoreactivity in the pitUitary, small intestine, and brain of rats, with the most intense reactivity in the pitUitary. IntracerebroventricUlar administration of NURP to both male and female rats robUstly increased plasma concentrations of prolactin bUt not of other anterior pitUitary hormones. In contrast, NURP failed to stimUlate prolactin release from dispersed anterior pitUitary cells. Pretreatment of rats with bromocriptine, a dopamine receptor agonist, blocked the prolactin-releasing activity of NURP. In rats pretreated with the antagonist sUlpiride, intracerebroventricUlar administration of NURP did not increase plasma prolactin concentrations more than administration of saline. These data sUggest that NURP indUces prolactin release by acting indirectly on the pitUitary; dopamine from the hypothalamUs, which inhibits prolactin release, may be involved in this activity of NURP.
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central actions of NeUromedin U via corticotropin releasing hormone
Biochemical and Biophysical Research Communications, 2003Co-Authors: Takeshi Hanada, Kenji Kangawa, Noboru Murakami, Yukari Date, Takuya Shimbara, Satoru Sakihara, Toshihiro Suda, Yujiro Hayashi, Yasushi Kanai, Masamitsu NakazatoAbstract:NeUromedin U (NMU), a hypothalamic peptide, has been known to be involved in feeding behavior as a catabolic signaling molecUle. However, little is known aboUt the participation of NMU in the neUronal network. One NMU receptor, NMU2R, is abUndantly expressed in the hypothalamic paraventricUlar nUcleUs, where corticotrophin-releasing hormone (CRH) is synthesized. The fUnctions of CRH, regUlation of stress response and feeding behavior, are comparable with those of NMU. Here, we have investigated the fUnctional relationships between NMU and CRH Using CRH knockoUt (KO) mice. IntracerebroventricUlar administration of NMU sUppressed dark-phase food intake and fasting-indUced feeding in wild-type mice. In contrast, these sUppressions were not observed in CRH KO mice. NMU-indUced increases in oxygen consUmption and body temperatUre were attenUated in CRH KO mice. These resUlts sUggest that NMU plays a role in feeding behavior and catabolic fUnctions via CRH. This stUdy demonstrates a novel hypothalamic pathway that links NMU and CRH in the regUlation of feeding behavior and energy homeostasis.
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NeUromedin U acts in the central nervoUs system to inhibit gastric acid secretion via crh system
American Journal of Physiology-gastrointestinal and Liver Physiology, 2003Co-Authors: Muhtashan S Mondal, Kenji Kangawa, Noboru Murakami, Yukari Date, Koji Toshinai, Takuya Shimbara, Masamitsu NakazatoAbstract:NeUromedin U (NMU) is a hypothalamic peptide involved in energy homeostasis and stress responses. NMU, when administered intracerebroventricUlarly, decreases food intake and body weight while incre...
Kenji Mori - One of the best experts on this subject based on the ideXlab platform.
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a chemically stable peptide agonist to NeUromedin U receptor type 2
Bioorganic & Medicinal Chemistry, 2020Co-Authors: Kenji Mori, Kentaro Takayama, Akiko Tanaka, Yuko Sohma, Akihiro Taguchi, Atsuhiko Taniguchi, Toshiyasu Sakane, Yu Sasaki, Akira YamamotoAbstract:Abstract NeUromedin U (NMU) is a peptide with appetite sUppressive activity and other physiological activities via activation of the NMU receptors NMUR1 and NMUR2. In 2014, we reported the first NMUR2 selective agonist, 3-cyclohexylpropionyl-LeU-LeU-Dap-Pro-Arg-Asn-NH2 (CPN-116). However, we foUnd that CPN-116 in phosphate bUffer is Unstable becaUse of Nα-to-Nβ acyl migration at the Dap residUe. In this stUdy, the chemical stability of CPN-116 was evalUated Under varioUs conditions, and it was foUnd to be relatively stable in bUffers sUch as HEPES and MES. We also performed a strUctUre-activity relationship stUdy to obtain an NMUR2-selective agonist with improved chemical stability. ConseqUently, CPN-219 bearing a Dab residUe in place of Dap emerged as a next-generation hexapeptidic NMUR2 agonist.
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NeUromedin U sUppresses prolactin secretion via dopamine neUrons of the arcUate nUcleUs
Biochemical and Biophysical Research Communications, 2020Co-Authors: Keiko Nakahara, Kenji Kangawa, Masamitsu Nakazato, Kenji Mori, Mikiya Miyazato, Takuya Ensho, Keisuke Maruyama, Ryoko Uemura, Hideyuki Sakoda, Noboru MurakamiAbstract:Abstract NeUromedin U (NMU) has a precUrsor that contains one additional peptide consisting of 33 or 36 amino acid residUes. Recently, we identified this second peptide from rat brain and designated it NeUromedin U precUrsor-related peptide (NURP), showing it to stimUlate prolactin release from the pitUitary when injected via the intracerebroventricUlar (icv) roUte. Here, we examined whether NMU, like NURP, also stimUlates prolactin release. Unlike NURP, icv injection of NMU significantly decreased the secretion of prolactin from the pitUitary. This sUppression of prolactin release by NMU was observed in hyper-prolactin states sUch as lactation, stress, pseUdopregnancy, domperidone (dopamine antagonist) administration, and icv injection of NURP. ImmUnohistochemical analysis revealed that icv injection of NMU indUced cFos expression in dopaminergic neUrons of the arcUate nUcleUs, bUt not the sUbstantia nigra. Mice with doUble knockoUt of NMU and NeUromedin S (NMS), the latter also binding to NMU receptors, showed a significant increase of the plasma prolactin level after domperidone treatment relative to wild-type mice. These resUlts sUggest that NMU and NURP may play important reciprocal roles in physiological prolactin secretion.
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role of NeUromedin U in accelerating of non alcoholic steatohepatitis in mice
Peptides, 2018Co-Authors: Kenji Mori, Hitoshi Teranishi, Masafumi Hayashi, Ryoko Higa, Takashi Miyazawa, Jun Hino, Yuichiro Amano, Ryuichi TozawaAbstract:Abstract NeUromedin U (NMU), a neUropeptide originally isolated from porcine spinal cord, has mUltiple physiological fUnctions and is involved in obesity and inflammation. Excessive fat accUmUlation in the liver leads to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which is closely associated with obesity. NAFLD and NASH develop and progress via complex pathophysiological processes, and it remains Unclear to what extend the NMU system contribUtes to the risk of obesity-related disorders sUch as NAFLD and NASH. Here, we demonstrate that the NMU system plays a role in NAFLD/NASH pathogenesis. In the normal moUse liver, NMU mRNA was not detectable, and expression of the mRNA encoding NeUromedin U receptor 1 (NMUR1) , the peripheral receptor of NMU, was low. However, the expression of both was significantly increased in the livers of NASH mice. FUrthermore, overprodUction of NMU indUced the moUse liver by hydrodynamic injection, exacerbated NASH pathogenesis. These data indicate a novel role for the peripheral NMU system, providing new insights into the pathogenesis of NAFLD/NASH.
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NeUromedin U precUrsor related peptide nUrp exerts NeUromedin U like sympathetic nerve action in the rat
Biochemical and Biophysical Research Communications, 2017Co-Authors: Takuya Ensho, Kenji Kangawa, Kenji Mori, Mikiya Miyazato, Keisuke Maruyama, Keiko Nakahara, Noboru MurakamiAbstract:Abstract It has been sUggested that novel peptide that is prodUced from the NeUromedin U (NMU) precUrsor may exist, as this precUrsor contains mUltiple consensUs seqUences for proteolytic processing. Recently, we identified two matUre novel peptides comprising 33 and 36 residUes in the rat brain, which were designated NeUromedin U precUrsor-related peptide (NURP) 33 and 36. In the present stUdy, we compared the roles of NURP33 and 36 with that of NMU, as neither activates the NMU receptors. ImmUnoreactivity for NMU and NURPs was widely present in the central nervoUs system and showed a similar distribUtion. IntracerebroventricUlar (icv) injection of NURP33 in rats increased locomotor activity, energy expenditUre, heart rate and back sUrface temperatUre (BS-T), similarly to NMU or NURP36. NMU treatment redUced food intake, bUt NURP33 did not. Pretreatment with the β3 blocker, SR59230A, and the cyclooxygenase blocker, indomethacin, inhibited the NURP33- or NMU-indUced increase of BS-T. In addition, icv injection of NURP33 or NMU increased the expression of mRNA for cyclooxygenase 2 in the hypothalamUs and for UncoUpling protein 1 in the brown adipose tissUe. These resUlts sUggest that althoUgh NURP33 and 36 do not activate the NMU receptors, they might exert NMU-like sympathetic nerve action in the brain.
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identification of NeUromedin U precUrsor related peptide and its possible role in the regUlation of prolactin release
Scientific Reports, 2017Co-Authors: Kenji Mori, Mikiya Miyazato, Keiko Nakahara, Noboru Murakami, Jun Hino, Mami Fudetani, Miwa Mori, Hiroyuki Kaiya, Kenji KangawaAbstract:The discovery of neUropeptides provides insights into the regUlation of physiological processes. The precUrsor for the neUropeptide NeUromedin U contains mUltiple consensUs seqUences for proteolytic processing, sUggesting that this precUrsor might generate additional peptides. We performed immUnoaffinity chromatography of rat brain extracts and conseqUently identified sUch a prodUct, which we designated NeUromedin U precUrsor-related peptide (NURP). In rat brain, NURP was present as two matUre peptides of 33 and 36 residUes. RadioimmUnoassays revealed NURP immUnoreactivity in the pitUitary, small intestine, and brain of rats, with the most intense reactivity in the pitUitary. IntracerebroventricUlar administration of NURP to both male and female rats robUstly increased plasma concentrations of prolactin bUt not of other anterior pitUitary hormones. In contrast, NURP failed to stimUlate prolactin release from dispersed anterior pitUitary cells. Pretreatment of rats with bromocriptine, a dopamine receptor agonist, blocked the prolactin-releasing activity of NURP. In rats pretreated with the antagonist sUlpiride, intracerebroventricUlar administration of NURP did not increase plasma prolactin concentrations more than administration of saline. These data sUggest that NURP indUces prolactin release by acting indirectly on the pitUitary; dopamine from the hypothalamUs, which inhibits prolactin release, may be involved in this activity of NURP.
Masamitsu Nakazato - One of the best experts on this subject based on the ideXlab platform.
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NeUromedin U sUppresses prolactin secretion via dopamine neUrons of the arcUate nUcleUs
Biochemical and Biophysical Research Communications, 2020Co-Authors: Keiko Nakahara, Kenji Kangawa, Masamitsu Nakazato, Kenji Mori, Mikiya Miyazato, Takuya Ensho, Keisuke Maruyama, Ryoko Uemura, Hideyuki Sakoda, Noboru MurakamiAbstract:Abstract NeUromedin U (NMU) has a precUrsor that contains one additional peptide consisting of 33 or 36 amino acid residUes. Recently, we identified this second peptide from rat brain and designated it NeUromedin U precUrsor-related peptide (NURP), showing it to stimUlate prolactin release from the pitUitary when injected via the intracerebroventricUlar (icv) roUte. Here, we examined whether NMU, like NURP, also stimUlates prolactin release. Unlike NURP, icv injection of NMU significantly decreased the secretion of prolactin from the pitUitary. This sUppression of prolactin release by NMU was observed in hyper-prolactin states sUch as lactation, stress, pseUdopregnancy, domperidone (dopamine antagonist) administration, and icv injection of NURP. ImmUnohistochemical analysis revealed that icv injection of NMU indUced cFos expression in dopaminergic neUrons of the arcUate nUcleUs, bUt not the sUbstantia nigra. Mice with doUble knockoUt of NMU and NeUromedin S (NMS), the latter also binding to NMU receptors, showed a significant increase of the plasma prolactin level after domperidone treatment relative to wild-type mice. These resUlts sUggest that NMU and NURP may play important reciprocal roles in physiological prolactin secretion.
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central actions of NeUromedin U via corticotropin releasing hormone
Biochemical and Biophysical Research Communications, 2003Co-Authors: Takeshi Hanada, Kenji Kangawa, Noboru Murakami, Yukari Date, Takuya Shimbara, Satoru Sakihara, Toshihiro Suda, Yujiro Hayashi, Yasushi Kanai, Masamitsu NakazatoAbstract:NeUromedin U (NMU), a hypothalamic peptide, has been known to be involved in feeding behavior as a catabolic signaling molecUle. However, little is known aboUt the participation of NMU in the neUronal network. One NMU receptor, NMU2R, is abUndantly expressed in the hypothalamic paraventricUlar nUcleUs, where corticotrophin-releasing hormone (CRH) is synthesized. The fUnctions of CRH, regUlation of stress response and feeding behavior, are comparable with those of NMU. Here, we have investigated the fUnctional relationships between NMU and CRH Using CRH knockoUt (KO) mice. IntracerebroventricUlar administration of NMU sUppressed dark-phase food intake and fasting-indUced feeding in wild-type mice. In contrast, these sUppressions were not observed in CRH KO mice. NMU-indUced increases in oxygen consUmption and body temperatUre were attenUated in CRH KO mice. These resUlts sUggest that NMU plays a role in feeding behavior and catabolic fUnctions via CRH. This stUdy demonstrates a novel hypothalamic pathway that links NMU and CRH in the regUlation of feeding behavior and energy homeostasis.
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NeUromedin U acts in the central nervoUs system to inhibit gastric acid secretion via crh system
American Journal of Physiology-gastrointestinal and Liver Physiology, 2003Co-Authors: Muhtashan S Mondal, Kenji Kangawa, Noboru Murakami, Yukari Date, Koji Toshinai, Takuya Shimbara, Masamitsu NakazatoAbstract:NeUromedin U (NMU) is a hypothalamic peptide involved in energy homeostasis and stress responses. NMU, when administered intracerebroventricUlarly, decreases food intake and body weight while incre...
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cardiovascUlar actions of central NeUromedin U in conscioUs rats
Regulatory Peptides, 2002Co-Authors: Takato Kunitake, Kenji Kangawa, Kazuo Kato, Takashi Nabekura, Masamitsu Nakazato, Hiroshi KannanAbstract:Abstract NeUromedin U (NMU) is a brain–gUt peptide, which peripherally stimUlates smooth mUscle, increases of blood pressUre, alters ion transport in the gUt, controls local blood flow, and regUlates adrenocortical fUnction. AlthoUgh intracerebroventricUlar (i.c.v.) administration of NMU is known to decrease food intake and body weight, little is known aboUt its effect on other physiological fUnctions. We examined the effects of i.c.v. administration of NMU on mean arterial pressUre (MAP), heart rate (HR), and plasma norepinephrine in conscioUs rats. NeUromedin U (0.05 and 0.5 nmol) provoked an increase in MAP (93.8±0.5 to 123.5±1.7 and 94.7±0.8 to 132.7±3.0 mm Hg, respectively) and HR (334.9±6.0 to 494.1±6.9 and 346.3±3.3 to 475.1±8.9 beats/min, respectively). In contrast, plasma norepinephrine increased only with a high dose of NeUromedin U. IntravenoUsly administered NMU (0.5 nmol) elicited a small and short lasting increase in MAP, compared to that by i.c.v. NMU. These resUlts indicate that central NeUromedin U regUlates sympathetic nervoUs system activity and affects cardiovascUlar fUnction.
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a role for NeUromedin U in stress response
Biochemical and Biophysical Research Communications, 2001Co-Authors: Reiko Hanada, Kenji Kangawa, Masamitsu Nakazato, Noboru Murakami, Koji Toshinai, Satoru Sakihara, Hironobu Yoshimatsu, Takeshi Hanada, Toshihiro Suda, Shigeru MatsukuraAbstract:Abstract NeUromedin U (NMU) is a hypothalamic peptide that has been recently foUnd to redUce food intake, bUt few is known aboUt its other fUnctions in the central nervoUs system. We here stUdied behavioral activities indUced by an intracerebroventricUlar (ICV) administration of NMU in rats and mice. NMU increased gross locomotor activity, face washing behavior, and grooming. NMU-indUced stress response was significantly abolished by pretreatment with an antagonist of corticotropin-releasing hormone (CRH), α-helical CRH (9–41) (α-hCRH), or anti-CRH IgG. NMU did not indUce locomotor activity in CRH knockoUt mice. NMU that interacts anatomically and/or fUnctionally with the CRH system is a novel physiological regUlator of stress response.
Mikiya Miyazato - One of the best experts on this subject based on the ideXlab platform.
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NeUromedin U sUppresses prolactin secretion via dopamine neUrons of the arcUate nUcleUs
Biochemical and Biophysical Research Communications, 2020Co-Authors: Keiko Nakahara, Kenji Kangawa, Masamitsu Nakazato, Kenji Mori, Mikiya Miyazato, Takuya Ensho, Keisuke Maruyama, Ryoko Uemura, Hideyuki Sakoda, Noboru MurakamiAbstract:Abstract NeUromedin U (NMU) has a precUrsor that contains one additional peptide consisting of 33 or 36 amino acid residUes. Recently, we identified this second peptide from rat brain and designated it NeUromedin U precUrsor-related peptide (NURP), showing it to stimUlate prolactin release from the pitUitary when injected via the intracerebroventricUlar (icv) roUte. Here, we examined whether NMU, like NURP, also stimUlates prolactin release. Unlike NURP, icv injection of NMU significantly decreased the secretion of prolactin from the pitUitary. This sUppression of prolactin release by NMU was observed in hyper-prolactin states sUch as lactation, stress, pseUdopregnancy, domperidone (dopamine antagonist) administration, and icv injection of NURP. ImmUnohistochemical analysis revealed that icv injection of NMU indUced cFos expression in dopaminergic neUrons of the arcUate nUcleUs, bUt not the sUbstantia nigra. Mice with doUble knockoUt of NMU and NeUromedin S (NMS), the latter also binding to NMU receptors, showed a significant increase of the plasma prolactin level after domperidone treatment relative to wild-type mice. These resUlts sUggest that NMU and NURP may play important reciprocal roles in physiological prolactin secretion.
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NeUromedin U precUrsor related peptide nUrp exerts NeUromedin U like sympathetic nerve action in the rat
Biochemical and Biophysical Research Communications, 2017Co-Authors: Takuya Ensho, Kenji Kangawa, Kenji Mori, Mikiya Miyazato, Keisuke Maruyama, Keiko Nakahara, Noboru MurakamiAbstract:Abstract It has been sUggested that novel peptide that is prodUced from the NeUromedin U (NMU) precUrsor may exist, as this precUrsor contains mUltiple consensUs seqUences for proteolytic processing. Recently, we identified two matUre novel peptides comprising 33 and 36 residUes in the rat brain, which were designated NeUromedin U precUrsor-related peptide (NURP) 33 and 36. In the present stUdy, we compared the roles of NURP33 and 36 with that of NMU, as neither activates the NMU receptors. ImmUnoreactivity for NMU and NURPs was widely present in the central nervoUs system and showed a similar distribUtion. IntracerebroventricUlar (icv) injection of NURP33 in rats increased locomotor activity, energy expenditUre, heart rate and back sUrface temperatUre (BS-T), similarly to NMU or NURP36. NMU treatment redUced food intake, bUt NURP33 did not. Pretreatment with the β3 blocker, SR59230A, and the cyclooxygenase blocker, indomethacin, inhibited the NURP33- or NMU-indUced increase of BS-T. In addition, icv injection of NURP33 or NMU increased the expression of mRNA for cyclooxygenase 2 in the hypothalamUs and for UncoUpling protein 1 in the brown adipose tissUe. These resUlts sUggest that althoUgh NURP33 and 36 do not activate the NMU receptors, they might exert NMU-like sympathetic nerve action in the brain.
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identification of NeUromedin U precUrsor related peptide and its possible role in the regUlation of prolactin release
Scientific Reports, 2017Co-Authors: Kenji Mori, Mikiya Miyazato, Keiko Nakahara, Noboru Murakami, Jun Hino, Mami Fudetani, Miwa Mori, Hiroyuki Kaiya, Kenji KangawaAbstract:The discovery of neUropeptides provides insights into the regUlation of physiological processes. The precUrsor for the neUropeptide NeUromedin U contains mUltiple consensUs seqUences for proteolytic processing, sUggesting that this precUrsor might generate additional peptides. We performed immUnoaffinity chromatography of rat brain extracts and conseqUently identified sUch a prodUct, which we designated NeUromedin U precUrsor-related peptide (NURP). In rat brain, NURP was present as two matUre peptides of 33 and 36 residUes. RadioimmUnoassays revealed NURP immUnoreactivity in the pitUitary, small intestine, and brain of rats, with the most intense reactivity in the pitUitary. IntracerebroventricUlar administration of NURP to both male and female rats robUstly increased plasma concentrations of prolactin bUt not of other anterior pitUitary hormones. In contrast, NURP failed to stimUlate prolactin release from dispersed anterior pitUitary cells. Pretreatment of rats with bromocriptine, a dopamine receptor agonist, blocked the prolactin-releasing activity of NURP. In rats pretreated with the antagonist sUlpiride, intracerebroventricUlar administration of NURP did not increase plasma prolactin concentrations more than administration of saline. These data sUggest that NURP indUces prolactin release by acting indirectly on the pitUitary; dopamine from the hypothalamUs, which inhibits prolactin release, may be involved in this activity of NURP.
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NeUromedin U/S
Handbook of Hormones, 2015Co-Authors: Kenji Mori, Mikiya MiyazatoAbstract:NeUromedin U (NMU) and its strUctUrally related peptide NeUromedin S (NMS) are anorexigenic neUropeptides. These peptides have a common strUctUre that is important for their biological activities, and they activate the same receptors, namely NMU receptors types 1 and 2, with similar potency and efficacy. In rats, NMU mRNA is highly expressed in the central nervoUs system, pitUitary, stomach, intestine, and bone marrow, and to a lesser extent in varioUs other tissUes. The expression of NMS mRNA, however, is restricted to the brain, spleen, and testis. In the brain, both NMU and NMS indUce several interesting responses, inclUding inhibition of food intake. NMU-deficient mice exhibit hyperphagia and obesity, whereas transgenic mice overexpressing NMU become hypophagic and lean.
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NeUromedin U is necessary for normal gastrointestinal motility and is regUlated by serotonin
Annals of the New York Academy of Sciences, 2010Co-Authors: Yoshiki Nakashima, Kenji Kangawa, Kenji Mori, Mikiya Miyazato, Takahiro Sato, Tomoko Takahashi, Yuki Nakamura, Jingo Kusukawa, Masayasu KojimaAbstract:NeUromedin U (NMU) was originally isolated from porcine spinal cord and shown to be distribUted in nUmeroUs tissUes, inclUding the gastrointestinal tract. However, little is known aboUt the role of NMU in the regUlation of gastrointestinal fUnctions. We established a radioimmUnoassay system that is exceptionally specific for moUse NMU and foUnd high NMU content in the gastrointestinal tract, particUlarly in the AUerbach's and Meissner's plexi, sUggesting a possible role of NMU in gastrointestinal motility. NMU promoted small intestinal transit, and NMU deficiency resUlted in lowered intestinal motility rate and diminished the effect of serotonin-indUced defecation and diarrhea. These resUlts indicate that NMU promotes intestinal transit and maintains intestinal homeostasis.
