Faculty Profiles - AIZAWA Sayaka

Papers - AIZAWA Sayaka

Division display 1 - 20 of about 29 ／ All the affair displays >>

Neuromedin U-deficient rats do not lose body weight or food intake. Reviewed International journal

Kyoka Yokogi, Yuki Goto, Mai Otsuka, Fumiya Ojima, Tomoe Kobayashi, Yukina Tsuchiba, Yu Takeuchi, Masumi Namba, Mayumi Kohno, Minami Tetsuka, Sakae Takeuchi, Makoto Matsuyama, Sayaka Aizawa

Scientific reports 12 ( 1 ) 17472 - 17472 2022.10

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Studies in genetically modified mice establish that essential roles of endogenous neuromedin U (NMU) are anorexigenic function and metabolic regulation, indicating that NMU is expected to be a potential target for anti-obesity agents. However, in central administration experiments in rats, inconsistent results have been obtained, and the essential role of NMU energy metabolism in rats remain unclear. This study aims to elucidate the role of endogenous NMU in rats. We generated NMU knockout (KO) rats that unexpectedly showed no difference in body weight, adiposity, circulating metabolic markers, body temperature, locomotor activity, and food consumption in both normal and high fat chow feeding. Furthermore, unlike reported in mice, expressions of Nmu and NMU receptor type 2 (Nmur2) mRNA were hardly detectable in the rat hypothalamic nuclei regulating feeding and energy metabolism, including the arcuate nucleus and paraventricular nucleus, while Nmu was expressed in pars tuberalis and Nmur2 was expressed in the ependymal cell layer of the third ventricle. These results indicate that the species-specific expression pattern of Nmu and Nmur2 may allow NMU to have distinct functions across species, and that endogenous NMU does not function as an anorexigenic hormone in rats.

DOI： 10.1038/s41598-022-21764-6

Identification of pennaceous barbule cell factor (PBCF), a novel gene with spatiotemporal expression in barbule cells during feather development

Minori Nakaoka, Hibiki Fukuchi, Maho Ogoshi, Sayaka Aizawa, Sakae Takeuchi

Gene 941 149244 - 149244 2025.3

Crosstalk between prolactin, insulin-like growth factors, and thyroid hormones in feather growth regulation in neonatal chick wings, Reviewed

Yuri Nozawa, Ayako Okamura, Hibiki Fukuchi, Masamichi Shinohara, Sayaka Aizawa, Sakae Takeuchi

General and Comparative Endocrinology, 2024, 114657, ISSN 0016-6480 2024.12

Revisiting the hormonal control of sexual dimorphism in chicken feathers. International journal

Li You, Kaori Nishio, Kinue Kowata, Minaru Horikawa, Hibiki Fukuchi, Maho Ogoshi, Sayaka Aizawa, Sakae Takeuchi

General and comparative endocrinology 114601 - 114601 2024.8

Language：English Publishing type：Research paper (scientific journal)

Sexual dimorphism in plumage is widespread among avian species. In chickens, adult females exhibit countershading, characterized by dull-colored round feathers lacking fringe on the saddle, while adult males display vibrant plumage with deeply fringed bright feathers. This dimorphism is estrogen-dependent, and administering estrogen to males transforms their showy plumage into cryptic female-like plumage. Extensive studies have shown that estrogen's role in female plumage formation requires thyroid hormone; however, the precise mechanisms of their interaction remain unclear. In this study, we investigated the roles of estrogen and thyroid hormone in creating sexual dimorphism in the structure and coloration of saddle feathers by administering each hormone to adult males and observing the resulting changes in regenerated feathers induced by plucking. RT-PCR analysis revealed that the expression of type 3 deiodinase (DIO3), responsible for thyroid hormone inactivation, correlates with fringing. Estrogen suppressed DIO3 and agouti signaling protein (ASIP) expression while stimulating BlSK1, a marker of barbule cells, resulting in female-like feathers with mottled patterns and lacking fringes. Administration of thyroxine (T4) stimulated BlSK1 and proopiomelanocortin (POMC) expression, with no effect on ASIP, leading to the formation of solid black feathers lacking fringes. Triiodothyronine (T3) significantly increased POMC expression in pulp cells in culture. Taken together, these findings suggest that estrogen promotes the formation of solid vanes by suppressing DIO3 expression, while also inducing the formation of mottled patterns through inhibition of ASIP expression and indirect stimulation of melanocortin expression via changes in local T3 concentration. This is the first report describing molecular mechanism underlying hormonal crosstalk in creating sexual dimorphism in feathers.

DOI： 10.1016/j.ygcen.2024.114601

A regulatory mechanism of mouse kallikrein 1 gene expression by estrogen

Takumi Iwasaki, Megumi Tokumori, Misaki Matsubara, Fumiya Ojima, Kana Kamigochi, Sayaka Aizawa, Maho Ogoshi, Atsushi P. Kimura, Sakae Takeuchi, Sumio Takahashi

Molecular and Cellular Endocrinology 577 112044 - 112044 2023.11

The suppressive effect of REVERBs on ghrelin and GOAT transcription in gastric ghrelin-producing cells Reviewed International journal

Mio Iijima, Shota Takemi, Sayaka Aizawa, Takafumi Sakai, Ichiro Sakata

Neuropeptides 90 102187 - 102187 2021.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

Ghrelin is a multifunctional gut peptide with a unique structure, which is modified by a medium chain fatty acid at the third serine by ghrelin O-acyl transferase (GOAT). It is well known that the major source of plasma ghrelin is the stomach, but the transcriptional regulation of gastric ghrelin and GOAT is incompletely understood. Here, we studied the involvement of the nuclear receptors REV-ERBα and REV-ERBβ on ghrelin and GOAT gene expression in vivo and in vitro. Reverse-transcriptase polymerase chain reaction analysis showed that REV-ERBα and REV-ERBβ mRNAs were expressed in the stomach and a stomach-derived ghrelin cell line (SG-1 cells). In vivo experiments with mice revealed the circadian rhythm of ghrelin, GOAT, and REV-ERBs. The peak expression of ghrelin and GOAT mRNAs occurred at Zeitgeber time (ZT) 4, whereas that of REV-ERBα and REV-ERBβ was observed at ZT8 and ZT12, respectively. Treatment of SG-1 cells with SR9009, a REV-ERB agonist, led to a significant reduction in ghrelin and GOAT mRNA levels. Overexpression of REV-ERBα and REV-ERBβ decreased ghrelin and GOAT mRNA levels in SG-1 cells. In contrast, small-interfering RNA (siRNA)-mediated double-knockdown of REV-ERBα and REV-ERBβ in SG-1 cells led to the upregulation in the expression of ghrelin and GOAT mRNAs. These results suggest that REV-ERBs suppress ghrelin and GOAT mRNA expression.

DOI： 10.1016/j.npep.2021.102187

Adrenomedullin 2 and 5 activate the calcitonin receptor-like receptor (clr) - Receptor activity-modifying protein 3 (ramp3) receptor complex in Xenopus tropicalis. Reviewed International journal

Maho Ogoshi, Mikoto Takahashi, Kota Aoyagi, Kazuyoshi Ukena, Sayaka Aizawa, Hideaki Takeuchi, Sumio Takahashi, Sakae Takeuchi

General and comparative endocrinology 306 113752 - 113752 2021.5

Language：English Publishing type：Research paper (scientific journal)

The adrenomedullin (AM) family is involved in diverse biological functions, including cardiovascular regulation and body fluid homeostasis, in multiple vertebrate lineages. The AM family consists of AM1, AM2, and AM5 in tetrapods, and the receptor for mammalian AMs has been identified as the complex of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2) or RAMP3. However, the receptors for AM in amphibians have not been identified. In this study, we identified the cDNAs encoding calcrl (clr), ramp2, and ramp3 receptor components from the western clawed frog (Xenopus tropicalis). Messenger RNAs of amphibian clr and ramp2 were highly expressed in the heart, whereas that of ramp3 was highly expressed in the whole blood. In HEK293T cells expressing clr-ramp2, cAMP response element luciferase (CRE-Luc) reporter activity was activated by am1. In HEK293T cells expressing clr-ramp3, CRE-Luc reporter activity was increased by the treatment with am2 at the lowest dose, but with am5 and am1 at higher dose. Our results provided new insights into the roles of AM family peptides through CLR-RAMP receptor complexes in the tetrapods.

DOI： 10.1016/j.ygcen.2021.113752

Adenosine stimulates neuromedin U mRNA expression in the rat pars tuberalis. Reviewed International journal

Sayaka Aizawa, Tingting Gu, Arisa Kaminoda, Ryuya Fujioka, Fumiya Ojima, Ichiro Sakata, Takafumi Sakai, Maho Ogoshi, Sumio Takahashi, Sakae Takeuchi

Molecular and cellular endocrinology 496 110518 - 110518 2019.10

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Neuromedin U (NMU) shows circadian expression in the rat pars tuberalis (PT), and is known to be suppressed by melatonin. Here we examined the involvement of adenosine in the regulation of Nmu expression. We found that the rat PT expressed adenosine receptor A2b and that an adenosine receptor agonist, NECA, stimulated Nmu expression in brain slice cultures. In vitro promoter assays revealed that NECA stimulated Nmu promoter activity via a cAMP response element (CRE) in the presence of adenosine receptor A2b. NECA also increased the levels of phosphorylated CRE-binding protein. These findings suggest that adenosine stimulates Nmu expression by activating the cAMP signaling pathway through adenosine receptor A2b in the rat PT. This is the first report to demonstrate that Nmu expression in the PT is regulated by adenosine, which acts as an intravital central metabolic signal, in addition to melatonin, which acts as an external photoperiodic environmental signal.

DOI： 10.1016/j.mce.2019.110518

Changes in prolactin receptor homodimer availability may cause late feathering in chickens. Reviewed International journal

Ayako Okamura, Ayane Masumoto, Atsushi Takenouchi, Toshiyuki Kudo, Sayaka Aizawa, Maho Ogoshi, Sumio Takahashi, Masaoki Tsudzuki, Sakae Takeuchi

General and comparative endocrinology 272 109 - 116 2019.2

Language：English Publishing type：Research paper (scientific journal)

Chicken early (EF) and late feathering (LF) are sex-linked phenotypes conferred by wild-type k+ and dominant K alleles on chromosome Z, respectively. Besides prolactin (PRL) receptor (PRLR) and sperm flagellar 2 (SPEF2) genes, the K allele contains a fusion gene in which partially duplicated PRLR (dPRLR) and SPEF2 (dSPEF2) genes are linked in a tail-to-tail manner. The causative dPRLR gene encodes a C-terminal truncated receptor. LF chickens have short or no primaries at hatching; however, their feather growth rate is higher than that of EF chickens. This study aimed to elucidate the molecular basis of the K allele's biphasic effect on feather development. By 3'RACE and RT-PCR analyses, we demonstrated that dSPEF2 gene transcription occurred beyond all coding exons of the dPRLR gene on the opposite strand and that dPRLR mRNA was less abundant than PRLR mRNA. In addition, a 5'UTR splice variant (SPV) of PRL receptor mRNAs was increased in LF chickens. In vitro expression analysis of 5'UTR linked to the luciferase reporter gene revealed higher translation efficiency of SPV. RT-qPCR showed that the dPRLR mRNA level was higher in embryos; conversely, SPV was higher in hatched chickens, as was dSPEF2 mRNA. These findings suggest that the K allele inhibits feather development at the fetal stage by expressing dPRLR to attenuate PRLR function and promotes feather growth after hatching by increasing PRLR through dSPEF2 mRNA expression. Increased SPV may cause greater feather growth than that in EF chickens by increasing the availability of PRLR homodimers and enhancing PRL signaling.

DOI： 10.1016/j.ygcen.2018.12.011

β-Oxidation in ghrelin-producing cells is important for ghrelin acyl-modification. Reviewed International journal

Chika Ikenoya, Shota Takemi, Arisa Kaminoda, Sayaka Aizawa, Shiomi Ojima, Zhi Gong, Rakhi Chacrabati, Daisuke Kondo, Reiko Wada, Toru Tanaka, Sachiko Tsuda, Takafumi Sakai, Ichiro Sakata

Scientific reports 8 ( 1 ) 9176 - 9176 2018.6

Language：English Publishing type：Research paper (scientific journal)

Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells. Treatment with an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) strongly decreased acylated ghrelin levels but did not affect ghrelin or ghrelin o-acyl transferase (GOAT) mRNA levels in PG-1 cells. Our results suggest that the medium-chain fatty acid used for the acyl-modification of ghrelin is produced in ghrelin-producing cells themselves by β-oxidation of long-chain fatty acids provided from the circulation.

DOI： 10.1038/s41598-018-27458-2

Milk basic protein increases ghrelin secretion and bone mineral density in rodents Reviewed

Yuko Ishida, Rakhi Chacrabati, Aiko Ono-Ohmachi, Zhi Gong, Chika Ikenoya, Sayaka Aizawa, Takayuki Y. Nara, Yoshikazu Morita, Ken Kato, Takafumi Sakai, Ichiro Sakata

Nutrition 39-40 15 - 19 2017.7

Identification of marker genes for pars tuberalis morphogenesis in chick embryo: expression of Cytokine-like 1 and Gap junction protein alpha 5 in pars tuberalis. Reviewed International journal

Sayaka Aizawa, Yuriko Higaki, Amrita Dudaui, Mai Nagasaka, Sumio Takahashi, Ichiro Sakata, Takafumi Sakai

Cell and tissue research 366 ( 3 ) 721 - 731 2016.12

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

The adenohypophysis is formed from the oral ectoderm and consists of the pars distalis (PD), pars intermedia, and pars tuberalis (PT). The mechanisms of PD development have been extensively studied, and the cellular differentiation of the PD is well understood. However, the morphogenesis and differentiation of the PT are still unclear, and the genes expressed during PT development remain largely unknown. We have explored genes specifically expressed in the PT during embryonic development and analyzed their spatiotemporal expression patterns. Microarray analysis of laser-captured PT and PD tissues obtained from chick embryos on embryonic day 10 (E10.0) has shown high expression of Cytokine-like 1 (CYTL1) and Gap junction protein alpha 5 (GJA5) genes in the PT. Detailed analysis of these spatiotemporal expression patterns during chick embryo development by in situ hybridization has revealed that CYTL1 mRNA first appears in the lateral head ectoderm and ventral head ectoderm at E1.5. The expression of CYTL1 moves into Rathke's pouch at E2.5 and is then localized in the PT primordium where it is continuously expressed until E12.0. GJA5 mRNA is transiently detected in the PT primordium from E6.0 to E12.0, whereas its expression is not detected in the PD during development. Thus, these genes might be involved in the regulation mechanisms of PT development and could be useful markers for PT development.

The proximal gastric corpus is the most responsive site of motilin-induced contractions in the stomach of the Asian house shrew. Reviewed International journal

Amrita Dudani, Sayaka Aizawa, Gong Zhi, Toru Tanaka, Takamichi Jogahara, Ichiro Sakata, Takafumi Sakai

Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology 186 ( 5 ) 665 - 75 2016.7

Language：English Publishing type：Research paper (scientific journal)

The migrating motor complex (MMC) is responsible for emptying the stomach during the interdigestive period, in preparation for the next meal. It is known that gastric phase III of MMC starts from the proximal stomach and propagates the contraction downwards. We hypothesized that a certain region of the stomach must be more responsive to motilin than others, and that motilin-induced strong gastric contractions propagate from that site. Stomachs of the Suncus or Asian house shrew, a small insectivorous mammal, were dissected and the fundus, proximal corpus, distal corpus, and antrum were examined to study the effect of motilin using an organ bath experiment. Motilin-induced contractions differed in different parts of the stomach. Only the proximal corpus induced gastric contraction even at motilin 10(-10) M, and strong contraction was induced by motilin 10(-9) M in all parts of the stomach. The GPR38 mRNA expression was also higher in the proximal corpus than in the other sections, and the lowest expression was observed in the antrum. GPR38 mRNA expression varied with low expression in the mucosal layer and high expression in the muscle layer. Additionally, motilin-induced contractions in each dissected part of the stomach were inhibited by tetrodotoxin and atropine pretreatment. These results suggest that motilin reactivity is not consistent throughout the stomach, and an area of the proximal corpus including the cardia is the most sensitive to motilin.

DOI： 10.1007/s00360-016-0985-1

TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis. Reviewed International journal

Sayaka Aizawa, Toru Okamoto, Yukari Sugiyama, Takahisa Kouwaki, Ayano Ito, Tatsuya Suzuki, Chikako Ono, Takasuke Fukuhara, Masahiro Yamamoto, Masayasu Okochi, Nobuhiko Hiraga, Michio Imamura, Kazuaki Chayama, Ryosuke Suzuki, Ikuo Shoji, Kohji Moriishi, Kyoji Moriya, Kazuhiko Koike, Yoshiharu Matsuura

Nature communications 7 11379 - 11379 2016.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Signal-peptide peptidase (SPP) is an intramembrane protease that participates in the production of the mature core protein of hepatitis C virus (HCV). Here we show that SPP inhibition reduces the production of infectious HCV particles and pathogenesis. The immature core protein produced in SPP-knockout cells or by treatment with an SPP inhibitor is quickly degraded by the ubiquitin-proteasome pathway. Oral administration of the SPP inhibitor to transgenic mice expressing HCV core protein (CoreTg) reduces the expression of core protein and ameliorates insulin resistance and liver steatosis. Moreover, the haploinsufficiency of SPP in CoreTg has similar effects. TRC8, an E3 ubiquitin ligase, is required for the degradation of the immature core protein. The expression of the HCV core protein alters endoplasmic reticulum (ER) distribution and induces ER stress in SPP/TRC8 double-knockout cells. These data suggest that HCV utilizes SPP cleavage to circumvent the induction of ER stress in host cells.

DOI： 10.1038/ncomms11379

Rikkunshitoinduces gastric relaxationviatheβ-adrenergic pathway inSuncus murinus Reviewed

A. Mondal, A. Takehara, S. Aizawa, T. Tanaka, N. Fujitsuka, T. Hattori, T. Sakai, I. Sakata

Neurogastroenterology & Motility 27 ( 6 ) 875 - 884 2015.6

G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro. Reviewed International journal

Zhi Gong, Makoto Yoshimura, Sayaka Aizawa, Reiko Kurotani, Jeffrey M Zigman, Takafumi Sakai, Ichiro Sakata

American journal of physiology. Endocrinology and metabolism 306 ( 1 ) E28-35 2014.1

Language：English Publishing type：Research paper (scientific journal)

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is produced predominantly in the stomach. It has been reported that endogenous ghrelin levels are increased by fasting and decreased immediately after feeding and that fasting-induced ghrelin release is controlled by the sympathetic nervous system. However, the mechanisms of plasma ghrelin decrement after feeding are poorly understood. Here, we studied the control of ghrelin secretion using ghrelin-producing cell lines and found that these cells express high levels of mRNA encoding G-protein coupled receptor 120 (GPR120). Addition of GW-9508 (a GPR120 chemical agonist) and α-linolenic acid (a natural ligand for GPR120) inhibited the secretion of ghrelin by ∼50 and 70%, respectively. However, the expression levels of preproghrelin and ghrelin O-acyltransferase (GOAT) mRNAs were not influenced by GW-9508. In contrast, the expression levels of prohormone convertase 1 were decreased significantly by GW-9508 incubation. Moreover, we observed that the inhibitory effect of GW-9508 on ghrelin secretion was blocked by a small interfering RNA (siRNA) targeting the sequence of GPR120. Furthermore, pretreatment with GW-9508 blocked the effect of the norepinephrine (NE)-induced ghrelin elevation in ghrelin cell lines. In addition, we showed that GW-9508 inhibited ghrelin secretion via extracellular signal-regulated kinase activity in ghrelin cell lines. Finally, we found that GW-9508 decreased plasma ghrelin levels in mice. These results suggest that the decrease of ghrelin secretion after feeding is induced partially by long-chain fatty acids that act directly on gastric GPR120-expressing ghrelin cells.

DOI： 10.1152/ajpendo.00306.2013

Detailed morphogenetic analysis of the embryonic chicken pars tuberalis as glycoprotein alpha subunit positive region. Reviewed International journal

Makiko Inoue, Sayaka Aizawa, Yuriko Higaki, Akira Kawashima, Kanako Koike, Hiroyasu Takagi, Takafumi Sakai, Ichiro Sakata

Journal of molecular histology 44 ( 4 ) 401 - 9 2013.8

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

The pars tuberalis (PT) is a part of the anterior pituitary gland that is located as a thin cell layer surrounding the median eminence. The characteristics of PT, including cell shape and cell composition, differ from those of the pars distalis (PD), suggesting that PT has unique physiological functions and different morphogenesis compared to PD. In this study, we used chicken embryos and showed for the first time that most hormone-producing cells in PT at embryonic day (E) 20.0 were only glycoprotein α subunit (αGSU)-positive staining cells. Then, using serial frontal and sagittal sections, we examined the detailed distribution of the αGSU mRNA-expressing region, as a marker of PT in the chicken embryonic pituitary gland during the E3.0-20.0 period. This three-dimensional expression pattern analysis clarified that αGSU mRNA expression initially appeared only in the bilateral regions of the Rathke's recess (RR) at E3.5, and this region expanded and showed a ring-like structure on RR. Subsequently, this αGSU mRNA-expressing region gradually expanded upward and reached the diencephalon at E8.0. This region became thinner as it surrounded the base of the diencephalon from E12.0 to E20.0. In this study, we demonstrated the detailed morphological changes of the chicken PT primordium by detecting αGSU mRNA, and we also showed that PT is a unique region in the early developmental stage.

DOI： 10.1007/s10735-012-9479-y

The role of the vagus nerve in the migrating motor complex and ghrelin- and motilin-induced gastric contraction in suncus. Reviewed International journal

Yuki Miyano, Ichiro Sakata, Kayuri Kuroda, Sayaka Aizawa, Toru Tanaka, Takamichi Jogahara, Reiko Kurotani, Takafumi Sakai

PloS one 8 ( 5 ) e64777 2013

Language：English Publishing type：Research paper (scientific journal)

The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating motor complex (MMC) in both dogs and humans during the fasted state. Feeding results in replacement of the MMC by a pattern of noncyclic, intermittent contractile activity termed as postprandial contractions. Although the MMC is known to be stimulated by motilin, recent studies have shown that ghrelin, which is from the same peptide family as motilin, is also involved in the regulation of the MMC. In the present study, we investigated the role of the vagus nerve on gastric motility using conscious suncus-a motilin- and ghrelin-producing small animal. During the fasted state, cyclic MMC comprising phases I, II, and III was observed in both sham-operated and vagotomized suncus; however, the duration and motility index (MI) of phase II was significantly decreased in vagotomized animals. Motilin infusion (50 ng·kg(-1)·min(-1) for 10 min) during phase I had induced phase III-like contractions in both sham-operated and vagotomized animals. Ghrelin infusion (0.1, 0.3, 1, 3, or 10 µg·kg(-1)·min(-1) for 10 min) enhanced the amplitude of phase II MMC in sham-operated animals, but not in vagotomized animals. After feeding, phase I was replaced by postprandial contractions, and motilin infusion (50 ng·kg(-1)·min(-1) for 10 min) did not induce phase III-like contractions in sham-operated suncus. However, in vagotomized suncus, feeding did not evoke postprandial contractions, but exogenous motilin injection strongly induced phase III-like contractions, as noted during the phase I period. Thus, the results indicate that ghrelin stimulates phase II of the MMC via the vagus nerve in suncus. Furthermore, the vagus nerve is essential for initiating postprandial contractions, and inhibition of the phase III-like contractions induced by motilin is highly dependent on the vagus nerve.

DOI： 10.1371/journal.pone.0064777

Mechanism of ghrelin-induced gastric contractions in Suncus murinus (house musk shrew): involvement of intrinsic primary afferent neurons. Reviewed International journal

Anupom Mondal, Sayaka Aizawa, Ichiro Sakata, Chayon Goswami, Sen-ichi Oda, Takafumi Sakai

PloS one 8 ( 4 ) e60365 2013

Language：English Publishing type：Research paper (scientific journal)

Here, we have reported that motilin can induce contractions in a dose-dependent manner in isolated Suncus murinus (house musk shrew) stomach. We have also shown that after pretreatment with a low dose of motilin (10(-10) M), ghrelin also induces gastric contractions at levels of 10(-10) M to 10(-7) M. However, the neural mechanism of ghrelin action in the stomach has not been fully revealed. In the present study, we studied the mechanism of ghrelin-induced contraction in vitro using a pharmacological method. The responses to ghrelin in the stomach were almost completely abolished by hexamethonium and were significantly suppressed by the administration of phentolamine, prazosin, ondansetron, and naloxone. Additionally, N-nitro-l-arginine methylester significantly potentiated the contractions. Importantly, the mucosa is essential for ghrelin-induced, but not motilin-induced, gastric contractions. To evaluate the involvement of intrinsic primary afferent neurons (IPANs), which are multiaxonal neurons that pass signals from the mucosa to the myenteric plexus, we examined the effect of the IPAN-related pathway on ghrelin-induced contractions and found that pretreatment with adenosine and tachykinergic receptor 3 antagonists (SR142801) significantly eliminated the contractions and GR113808 (5-hydroxytryptamine receptor 4 antagonist) almost completely eliminated it. The results indicate that ghrelin stimulates and modulates suncus gastric contractions through cholinergic, adrenergic, serotonergic, opioidergic neurons and nitric oxide synthases in the myenteric plexus. The mucosa is also important for ghrelin-induced gastric contractions, and IPANs may be the important interneurons that pass the signal from the mucosa to the myenteric plexus.

DOI： 10.1371/journal.pone.0060365

Negative regulation of neuromedin U mRNA expression in the rat pars tuberalis by melatonin. Reviewed International journal

Sayaka Aizawa, Ichiro Sakata, Mai Nagasaka, Yuriko Higaki, Takafumi Sakai

PloS one 8 ( 7 ) e67118 2013

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

The pars tuberalis (PT) is part of the anterior pituitary gland surrounding the median eminence as a thin cell layer. The characteristics of PT differ from those of the pars distalis (PD), such as cell composition and gene expression, suggesting that the PT has a unique physiological function compared to the PD. Because the PT highly expresses melatonin receptor type 1, it is considered a mediator of seasonal and/or circadian signals of melatonin. Expression of neuromedin U (NMU) that is known to regulate energy balance has been previously reported in the rat PT; however, the regulatory mechanism of NMU mRNA expression and secretion in the PT are still obscure. In this study, we examined both the diurnal change of NMU mRNA expression in the rat PT and the effects of melatonin on NMU in vivo. In situ hybridization and quantitative PCR analysis of laser microdissected PT samples revealed that NMU mRNA expression in the PT has diurnal variation that is high during the light phase and low during the dark phase. Furthermore, melatonin administration significantly suppressed NMU mRNA expression in the PT in vivo. On the other hand, 48 h fasting did not have an effect on PT-NMU mRNA expression, and the diurnal change of NMU mRNA expression was maintained. We also found the highest expression of neuromedin U receptor type 2 (NMUR2) mRNA in the third ventricle ependymal cell layer, followed by the arcuate nucleus and the spinal cord. These results suggest that NMU mRNA expression in the PT is downregulated by melatonin during the dark phase and shows diurnal change. Considering that NMU mRNA in the PT showed the highest expression level in the brain, PT-NMU may act on NMUR2 in the brain, especially in the third ventricle ependymal cell layer, with a circadian rhythm.

DOI： 10.1371/journal.pone.0067118

　 PREV - NEXT 　

1
2