Search PubMed⌕ Search

Biomedical subjects

Kenji Kangawa

Publications and source records attributed to Kenji Kangawa.

At least 91 records · Page 5Linked to original sources
PubMed2005

Adrenomedullin is up-regulated in nitrofen-induced fetal pulmonary hypoplasia.

BACKGROUND/PURPOSE: Pulmonary hypoplasia associated with congenital diaphragmatic hernia remains a major therapeutic problem. Adrenomedullin (AM), a multifunctional regulatory peptide, has been suggested to play a role in the mechanisms of fetal lung differentiation and maturation. The aim of this study was to investigate the pulmonary expression of AM in nitrofen-induced fetal pulmonary hypoplasia. MATERIALS AND METHODS: Pulmonary hypoplasia was induced in timed-pregnant Sprague-Dawley rats after administration of 100 mg nitrofen on day 9.5 of gestation. Fetal and neonatal lungs were excised on gestational days 16.5, 19, and 21 and 1 hour after birth and divided into the following 3 groups: nitrofen with diaphragmatic defect, nitrofen without diaphragmatic defect, and control (without nitrofen). Pulmonary levels of AM and AM messenger RNA expression were measured by radioimmunoassay and real time quantitative reverse transcriptase polymerase chain reaction, respectively. Localization of pulmonary AM was identified by immunohistochemical staining. RESULTS: There was a significant increase in pulmonary level of AM in the nitrofen-treated groups on gestational days 19 and 21. Real time quantitative reverse transcriptase polymerase chain reaction on gestational day 19 confirmed an increase of AM gene expression in the nitrofen-treated groups. Adrenomedullin immunoreactivity was more strongly expressed in airway epithelial cells in the nitrofen-treated groups than in the control. CONCLUSION: Nitrofen up-regulates expression of AM in the fetal lung, which suggests that AM has some pathophysiological role in the differentiation and/or maturation processes of pulmonary hypoplasia in congenital diaphragmatic hernia.

Abnormalities, Drug-Induced↗
PubMed2005

Olanzapine increases plasma ghrelin level in patients with schizophrenia.

OBJECTIVE: Increased appetite and weight gain are frequently reported in treatment with olanzapine. However, the mechanism behind this appetite gain remains unclear. Ghrelin is a newly discovered appetite-stimulating peptide that has a role in the regulation of feeding behavior. Ghrelin is synthesized principally in the stomach, and the concentration of circulating ghrelin is negatively correlated with leptin and body fat mass. To elucidate the mechanism of appetite and weight gain during olanzapine treatment, we investigated the circulating ghrelin levels. METHODS: Seven patients with schizophrenia were examined before and after 6-month administration of olanzapine. The concentrations of circulating ghrelin, leptin, glucose and lipid metabolic parameters were measured. RESULTS: Body fat percentage (P=0.0121) and serum leptin (P=0.0284) were significantly increased after 6-month administration of olanzapine. Both plasma total ghrelin (P=0.0188) and active ghrelin levels (P=0.0057) were significantly increased. Six of the seven patients reported increased appetite during olanzapine treatment. Other glucose and lipid parameters were not altered significantly. CONCLUSIONS: Although, the leptin level and body fat percentage were significantly increased, the concentration of circulating ghrelin was also significantly increased. Olanzapine may directly act on the secretion of ghrelin and induce appetite, resulting in weight gain.

Adult↗
PubMed2005

Different effects of peripheral and central ghrelin on regulation of food intake in the Japanese quail.

When rat or human ghrelin is administered to chickens or rats it stimulates the release of growth hormone, however, its effects on food intake differ between the two species. To investigate this discrepancy, we measured plasma ghrelin concentrations before and after food intake, and determined the effects of central (intracerebroventricular, icv) and peripheral (intraperitoneal, ip) injections of various ghrelin doses on food intake and body temperature in the Japanese quail. In control quails, plasma ghrelin levels were significantly increased in the fasting state; subsequent feeding produced a reduction, suggesting that ghrelin may act as an orexigenic signal in Japanese quails as well as mammals. Food intake was stimulated by ip, but not icv, injections of small doses of ghrelin, whereas both ip and icv injections of larger doses inhibited feeding. A large dose of ghrelin also increased body temperature. These results suggest that an increase in peripheral ghrelin may act as a hunger signal to induce food intake through stimulation of the afferent vagal nerve in the Japanese quail, as in rats, whereas central ghrelin may inhibit feeding in different ways in the two species.

Animals↗
PubMed2005

Plasma acylated ghrelin levels correlate with subjective symptoms of functional dyspepsia in female patients.

OBJECTIVE: Ghrelin is a brain-gut peptide that is mainly secreted from gastric endocrine cells (X/A like cells). In addition to promoting growth-hormone release and appetite, ghrelin also affects gastric motility and secretion. Circulating ghrelin levels are related to appetite and energy balance. Functional dyspepsia (FD) is a disorder characterized by the presence of chronic or recurrent symptoms of upper abdominal pain or discomfort. Although no known specific organic abnormalities are present in FD, abnormalities in gastrointestinal motility and sensitivity are thought to play a role in a substantial subgroup of patients. In addition, some patients also suffer from anorexia and body-weight loss. To investigate the role of ghrelin in the pathophysiology of FD, circulating ghrelin levels in affected patients were measured. MATERIAL AND METHODS: Eighteen Japanese female patients with functional dyspepsia and 18 healthy volunteers were recruited for the study. Acylated and desacyl forms of ghrelin were measured using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Although plasma levels of acylated or desacyl ghrelin were not significantly different between healthy subjects and FD patients, plasma acylated, but not desacyl ghrelin, levels were correlated with a subjective symptom score in FD patients. In addition, the ratio of acylated to desacyl ghrelin (A/D ratio) was correlated strongly with acylated, but not desacyl, ghrelin levels. CONCLUSIONS: The correlation of circulating acylated ghrelin levels with the subjective symptom score and the A/D ratio in FD patients suggest that acylated ghrelin may play a role in the pathophysiology of FD.

Adult↗
PubMed2005

Renoprotective effect of long-term combined treatment with adrenomedullin and omapatrilat in hypertensive rats.

BACKGROUND: Previous studies demonstrated that adrenomedullin (AM) is metabolized by neutral endopeptidases and that the renal effect of AM is augmented by the inhibition of neutral endopeptidases. We have recently shown that the long-term administration of AM has renoprotective effects. OBJECT: This study assessed the chronic renoprotective effects of AM combined with a vasopeptidase inhibitor in hypertensive rats and attempted to elucidate the mechanism involved. METHODS: We studied the following four groups: control Dahl salt-resistant (DR) rats, untreated Dahl salt-sensitive (DS) rats, omapatrilat (35 mg/kg per day)-treated DS rats; and human AM (500 ng/h) plus omapatrilat-treated DS rats. After 7 weeks' treatment, blood pressure, renal function, neurohumoral factors, gene expression levels, and histological findings were examined. RESULTS: DS rats were characterized by increased blood pressure, decreased renal function, abnormal histological findings, and increased gene expression of collagen I and III, transforming growth factor beta (TGF-beta), and NADPH oxidase subunits (p40phox, p47phox, and gp91phox) in the renal cortex compared with DR rats. Compared with DS rats, omapatrilat significantly decreased systolic blood pressure (-26 mmHg), improved renal function, histological findings, and messenger RNA expression levels of collagen I, collagen III, and TGF-beta. Combined treatment with omapatrilat and AM further improved renal function, histological findings, and mRNA expression levels of collagen I, collagen III, and TGF-beta, without a further reduction in blood pressure. Only combined treatment decreased mRNA levels of p40phox, p47phox, and gp91phox. There were no differences in plasma AM or atrial natriuretic peptide levels among three DS groups. CONCLUSION: Our results suggest that combined treatment with omapatrilat and AM provides additional renoprotective effects independent of blood pressure-lowering activity partly via inhibition of gene expressions of oxidative stress and extracellular matrix.

Adrenomedullin↗
PubMed2005

Adrenomedullin reflects cardiac dysfunction, excessive blood volume, and inflammation in hemodialysis patients.

BACKGROUND: Plasma adrenomedullin (AM) reflects cardiac dysfunction and predicts survival after myocardial infarction. The present study was designed to investigate whether the mature AM (mAM) reflects status of cardiac function, systemic blood volume, or inflammation in hemodialysis patients with cardiovascular disease, and whether mortality and additional cardiovascular morbidity can be predicted by mAM. METHODS: Plasma levels of mAM, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), norepinephrine (NE), and C-reactive protein (CRP) before hemodialysis were measured in 67 chronic hemodialysis patients with cardiovascular disease, along with 2-dimensional and Doppler echocardiographic variables. RESULTS: By univariate regression analysis, mAM correlated negatively with pulmonary venous flow velocity ratio and left ventricular (LV) ejection fraction and positively with LV inflow velocity ratio, LV end-diastolic, end-systolic volume indexes, plasma CRP level, and removal fluid volume by ultrafiltration. Multivariate stepwise regression analysis revealed that mAM reflected all variables better than log [ANP], log [BNP], and log [NE]. During a 1-year follow-up period, 7 patients died and 8 had additional cardiovascular events. Event-free Kaplan-Meier curves based on the median mAM (4.55 pmol/L) showed that patients with high plasma mAM levels had higher mortality and morbidity than those with low plasma mAM levels (P = 0.0056). By Cox multivariate proportional hazard analysis, mAM was related to mortality and morbidity [hazard ratio (HR) 4.55, 95% CI 1.2-16.8, P= 0.023). CONCLUSION: Plasma mAM reflects cardiac dysfunction, excessive blood volume, and inflammation better than ANP, BNP, and NE, resulting in a predictor of mortality and cardiovascular morbidity in hemodialysis patients with cardiovascular disease.

Adrenomedullin↗
PubMed2005

Cyclic AMP potentiates vascular endothelial cadherin-mediated cell-cell contact to enhance endothelial barrier function through an Epac-Rap1 signaling pathway.

Cyclic AMP (cAMP) is a well-known intracellular signaling molecule improving barrier function in vascular endothelial cells. Here, we delineate a novel cAMP-triggered signal that regulates the barrier function. We found that cAMP-elevating reagents, prostacyclin and forskolin, decreased cell permeability and enhanced vascular endothelial (VE) cadherin-dependent cell adhesion. Although the decreased permeability and the increased VE-cadherin-mediated adhesion by prostacyclin and forskolin were insensitive to a specific inhibitor for cAMP-dependent protein kinase, these effects were mimicked by 8-(4-chlorophenylthio)-2'-O-methyladenosine-3', 5'-cyclic monophosphate, a specific activator for Epac, which is a novel cAMP-dependent guanine nucleotide exchange factor for Rap1. Thus, we investigated the effect of Rap1 on permeability and the VE-cadherin-mediated cell adhesion by expressing either constitutive active Rap1 or Rap1GAPII. Activation of Rap1 resulted in a decrease in permeability and enhancement of VE-cadherin-dependent cell adhesion, whereas inactivation of Rap1 had the counter effect. Furthermore, prostacyclin and forskolin induced cortical actin rearrangement in a Rap1-dependent manner. In conclusion, cAMP-Epac-Rap1 signaling promotes decreased cell permeability by enhancing VE-cadherin-mediated adhesion lined by the rearranged cortical actin.

Actins↗
PubMed2005

Adrenomedullin: angiogenesis and gene therapy.

Adrenomedullin (AM) is a potent, long-lasting vasodilator peptide that was originally isolated from human pheochromocytoma. AM signaling is of particular significance in endothelial cell biology since the peptide protects cells from apoptosis, promotes angiogenesis, and affects vascular tone and permeability. The angiogenic effect of AM is mediated by activation of Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2, and focal adhesion kinase in endothelial cells. Both AM and its receptor, calcitonin receptor-like receptor, are upregulated through a hypoxia-inducible factor-1-dependent pathway under hypoxic conditions. Thus AM signaling plays an important role in the regulation of angiogenesis in hypoxic conditions. Recently, we have developed a nonviral vector, gelatin. Positively charged gelatin holds negatively charged plasmid DNA in its lattice structure. DNA-gelatin complexes can delay gene degradation, leading to efficient gene transfer. Administration of AM DNA-gelatin complexes induces potent angiogenic effects in a rabbit model of hindlimb ischemia. Thus gelatin-mediated AM gene transfer may be a new therapeutic strategy for the treatment of tissue ischemia. Endothelial progenitor cells (EPCs) play an important role in endothelial regeneration. Interestingly, EPCs phagocytose ionically linked DNA-gelatin complexes in coculture, which allows nonviral gene transfer into EPCs. AM gene transfer into EPCs inhibits cell apoptosis and induces proliferation and migration, suggesting that AM gene transfer strengthens the therapeutic potential of EPCs. Intravenous administration of AM gene-modified EPCs regenerate pulmonary endothelium, resulting in improvement of pulmonary hypertension. These results suggest that in vivo and in vitro transfer of AM gene using gelatin may be applicable for intractable cardiovascular disease.

Adrenomedullin↗
PubMed2005

Ghrelin: structure and function.

Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.

Amino Acid Sequence↗
PubMed2005

Circulating mature adrenomedullin is related to blood volume in full-term pregnancy.

Plasma adrenomedullin concentration increases during pregnancy. We measured blood volume and mature adrenomedullin concentration in plasma and cerebrospinal fluid and examined whether mature adrenomedullin in plasma and cerebrospinal fluid was associated with increasing blood volume during pregnancy. We enrolled 47 women undergoing surgery with spinal anesthesia in this study. We first measured mature adrenomedullin concentration in plasma and cerebrospinal fluid of nonpregnant women undergoing orthopedic surgery, pregnant women between 15 and 18 wk of gestation undergoing gynecological surgery, and pregnant women at full-term undergoing cesarean delivery. The second study included 20 healthy and full-term parturients scheduled for cesarean delivery. We measured arterial blood pressure and blood volume by noninvasive pulse spectrophotometry using indocyanine green. Plasma-mature adrenomedullin concentration was 1.24 +/- 0.98, 2.79 +/- 1.23, 4.79 +/- 2.61 fmol/mL (mean +/- sd) in the nonpregnant, the early gestation, and the full-term groups, respectively. But in cerebrospinal fluid, mature adrenomedullin did not significantly increase. Furthermore, mature adrenomedullin in plasma, but not cerebrospinal fluid, had a significant correlation with blood volume per unit body weight (r2= 0.46; P = 0.0009). These findings demonstrate that plasma-mature adrenomedullin concentration increased and that increased plasma-mature adrenomedullin is associated with increased blood volume during pregnancy.

Adrenomedullin↗
PubMed2005

Relationship between growth and plasma concentrations of ghrelin and growth hormone in juvenile beagle dogs.

Although the release of growth hormone (GH) is known to be regulated mainly by GH-releasing hormone (GHRH) and somatostatin (SRIF) secreted from the hypothalamus, ghrelin also may be involved in GH release during juvenile period. We have examined plasma concentrations of acylated ghrelin, desacyl ghrelin, and GH in juvenile beagle dogs. Plasma acylated and desacyl ghrelin levels changed through aging; however, there was no closely correlation between ghrelin, body weight and circulating GH levels during juvenile period. The increase in body weight was essentially linear until 8 months of age, whereas plasma GH concentrations exhibited bimodal peaks for the meanwhile. The results suggest that ghrelin may not play internal cueing in GH secretion in juvenile beagle dogs.

Age Factors↗
PubMed2005

Treatment of cachexia with ghrelin in patients with COPD.

STUDY OBJECTIVES: Ghrelin is a novel growth hormone (GH)-releasing peptide that also induces a positive energy balance by decreasing fat utility and stimulating feeding through GH-independent mechanisms. We investigated whether ghrelin improves cachexia and functional capacity in patients with COPD. METHODS: This is an open-label pilot study. Human ghrelin (2 microg/kg bid) was IV administered to seven cachectic patients with COPD for 3 weeks. Food intake, body composition, muscle strength, exercise capacity, pulmonary function, and sympathetic nerve activity were examined before and after ghrelin therapy. RESULTS: A single administration of ghrelin markedly increased serum GH (21-fold). Three-week treatment with ghrelin resulted in a significant increase in mean (+/- SEM) body weight (49.3 +/- 3.6 to 50.3 +/- 3.8 kg; p < 0.05). Food intake was significantly increased during ghrelin therapy. Ghrelin increased lean body mass and peripheral and respiratory muscle strength. Ghrelin significantly increased Karnofsky performance status score and the distance walked in 6 min (370 +/- 30 to 432 +/- 35 m; p < 0.05), although it did not significantly alter pulmonary function. Ghrelin attenuated the exaggerated sympathetic nerve activity, as indicated by a marked decrease in plasma norepinephrine level (889 +/- 123 to 597 +/- 116 pg/mL; p < 0.05). CONCLUSIONS: These preliminary results suggest that repeated administration of ghrelin improves body composition, muscle wasting, functional capacity, and sympathetic augmentation in cachectic patients with COPD.

Aged↗
PubMed2005

Plasma concentrations of adrenomedullin and ghrelin in hemodialysis patients with sustained and episodic hypotension.

Sustained and/or episodic hypotension during hemodialysis (HD) is an important clinical issue. Plasma adrenomedullin (AM) is increased in HD patients with sustained hypotension, but little is known about its implications for episodic hypotension. Ghrelin may also contribute to the pathophysiology of hypotension in HD patients. We evaluated plasma levels of AM and total ghrelin in sustained hypotensive (SH; n = 23), episodic hypotensive (EH; n = 30) and normotensive (NT; n = 23) HD patients. In the EH group, the relationship between low blood pressure during HD and circulating levels of AM and ghrelin was also evaluated. Plasma levels of AM were significantly higher in SH (34.3 +/- 8.3 fmol/ml, p<0.01) than in NT patients (27.6 +/- 5.2 fmol/ml), but not in EH patients (30.8 +/- 6.1 fmol/ml). There was no significant difference of plasma total ghrelin in SH (548.1 +/- 426.5 fmol/ml) and in EH patients (544.6 +/- 174.3 fmol/ml), compared with NT patients (400.0 +/- 219.7 fmol/ml). On the other hand, in EH patients, the "suppressed blood pressure ratio" during HD significantly correlated with plasma AM (r = 0.77, p<0.001) and with total ghrelin levels (r = 0.44, p<0.05). Our results suggest that ghrelin, as well as AM, may play an important role as vasodilator local hormones and regulation of blood pressure during HD, especially the occurrence of EH. Further studies are necessary to clarify the implication of these hormones in the control of hypotension during HD.

Adrenomedullin↗
PubMed2005

Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation.

The octanoylation of Ser3 is essential for the biological function of ghrelin. We examined the concentrations of the n-octanoylated active-form ghrelin in cord and neonatal blood using an RIA system that specifically recognized n-octanoylated ghrelin, as well as a system that measured the total ghrelin concentration. Plasma levels of active ghrelin in cord blood ranged from 7.7 to 38.4 pmol/l and correlated excellently with those of total ghrelin (r = 0.81, p<0.0001). The active ghrelin/total ghrelin (A/T) ratio ranged from 0.038 to 0.12 (median 0.072). The active ghrelin concentrations negatively correlated with birth body weight (r = -0.34, p = 0.01) and IGF-1 concentrations (r = -0.40, p = 0.003), but did not correlate with growth hormone (GH) concentrations. A considerable level of active ghrelin was detected in premature newborns. Venous cord blood samples showed a significantly higher active ghrelin concentration (p = 0.03) and A/T ratio (p = 0.01) than those in the artery. In neonatal blood, active ghrelin concentrations ranged from 4.6 to 22.6 pmol/l and the A/T ratio ranged from 0.02 to 0.081. These results demonstrate the existence of active-form ghrelin in fetal and neonatal circulation and may suggest the energy supply-dependent regulation of ghrelin expression/secretion in utero.

Birth Weight↗
PubMed2005

Influencing the between-feeding and endocrine responses of plasma ghrelin in healthy dogs.

OBJECTIVES: Ghrelin has recently been isolated from rat and human stomach as an endogenous ligand for the growth hormone (GH) secretagog receptor. Using beagle dogs, we investigated the distribution of ghrelin in the stomach and its possible role. METHODS: We examined: (i) GH release in response to ghrelin injection (0.5 or 5 microg/kg, i.v.), (ii) gastric localization of ghrelin-immunostained cells, (iii) changes in daily food consumption after ghrelin injection (3, 10, and 20 microg/kg, i.v.), (iv) plasma ghrelin levels under regular, but restricted feeding conditions, and (v) variations in plasma ghrelin levels in relatively lean, normal and obese dogs. RESULTS: Administration of ghrelin to dogs promptly increased circulating GH concentrations, although this effect was transitory and was maintained for only 20 min. Ghrelin was localized in the stomach fundus and body, but none was detected in either the pylorus or cardia. Administration of ghrelin at a dose of 20 microg/kg increased the daily food intake of beagle dogs. Plasma ghrelin levels peaked just before meal times, and then returned to basal levels. Obese dogs had higher plasma ghrelin levels than did normal and lean dogs. CONCLUSIONS: These results indicate that ghrelin is a potent GH secretagog in dogs. The distribution of ghrelin-immunoreactive cells in the canine stomach resembles that of both the murine and human stomach. Ghrelin participates in the control of feeding behavior and energy homeostasis in dogs and may, therefore, be involved in the development of obesity.

Animals↗
PubMed2004

Ghrelin directly regulates bone formation.

UNLABELLED: To clarify the role of ghrelin in bone metabolism, we examined the effect of ghrelin in vitro and in vivo. Ghrelin and its receptor, GHS-R1a, were identified in osteoblasts, and ghrelin promoted both proliferation and differentiation. Furthermore, ghrelin increased BMD in rats. Our results show that ghrelin directly affects bone formation. INTRODUCTION: Ghrelin is a gut peptide involved in growth hormone (GH) secretion and energy homeostasis. Recently, it has been reported that the adipocyte-derived hormone leptin, which also regulates energy homeostasis and opposes ghrelin's actions in energy homeostasis, plays a significant role in bone metabolism. This evidence implies that ghrelin may modulate bone metabolism; however, it has not been clarified. To study the role of ghrelin in skeletal integrity, we examined its effects on bone metabolism both in vitro and in vivo. MATERIALS AND METHODS: We measured the expression of ghrelin and growth hormone secretagogue receptor 1a (GHS-R1a) in rat osteoblasts using RT-PCR and immunohistochemistry (IHC). The effect of ghrelin on primary osteoblast-like cell proliferation was examined by recording changes in cell number and the level of DNA synthesis. Osteoblast differentiation markers (Runx2, collagen alpha1 type I [COLI], alkaline phosphatase [ALP], osteocalcin [OCN]) were analyzed using quantitative RT-PCR. We also examined calcium accumulation and ALP activity in osteoblast-like cells induced by ghrelin. Finally, to address the in vivo effects of ghrelin on bone metabolism, we examined the BMD of Sprague-Dawley (SD) rats and genetically GH-deficient, spontaneous dwarf rats (SDR). RESULTS: Ghrelin and GHS-R1a were identified in osteoblast-like cells. Ghrelin significantly increased osteoblast-like cell numbers and DNA synthesis in a dose-dependent manner. The proliferative effects of ghrelin were suppressed by [D-Lys(3)]-GHRP-6, an antagonist of GHS-R1a, in a dose-dependent manner. Furthermore, ghrelin increased the expression of osteoblast differentiation markers, ALP activity, and calcium accumulation in the matrix. Finally, ghrelin definitely increased BMD of both SD rats and SDRs. CONCLUSIONS: These observations show that ghrelin directly stimulates bone formation.

Adipocytes↗
PubMed2004

Endogenous neuromedin U has anorectic effects in the Japanese quail.

Neuromedin U (NMU), which is a brain-gut peptide, was first isolated as a smooth-muscle-contracting peptide from the porcine spinal cord in 1985. Intracerebroventricular (icv) injection of NMU into rats significantly reduced the food intake during dark period, and increased oxygen consumption, locomotor activity, and body temperature suggested that NMU is an anorectic and catabolic signaling molecule in mammals. In this study, we elucidated the central role of NMU in avian species using Japanese quail. Gene cloning analysis revealed that the amino acid sequence of Japanese quail NMU has high homology with that of chick, and low homology with that of rat except the C-terminal biologically active region. RT-PCR analysis revealed that NMU mRNA was expressed in various central and peripheral tissues. Both intraperitoneal (ip) and icv administration of synthetic Japanese quail NMU resulted in a significant reduction in food intake and increase in body temperature and locomotor activity in Japanese quails. Conversely, the administration of rat NMU into Japanese quail resulted in the opposite effects on food intake, body temperature, and locomotor activity. These opposite results may indicate that rat NMU act as an antagonist toward the Japanese quail NMU receptor. These results suggest that endogenous NMU plays an important role in the regulation of food intake and body temperature in avian species.

Amino Acid Sequence↗