Regulatory Peptides[JOURNAL]
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200 papers
Glucose-dependent insulinotropic polypeptide lowers branched chain amino acids in hyperglycemic rats.
Spégel P, Lindqvist A, Sandberg M … +1 more , Wierup N
Regul Pept · 2014 Feb · PMID 24412429 · Publisher ↗
Hypersecretion of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) has been associated with obesity and glucose intolerance. This condition has been suggested to be linked to GIP resistance. Beside...
Hypersecretion of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) has been associated with obesity and glucose intolerance. This condition has been suggested to be linked to GIP resistance. Besides its insulinotropic effect, GIP also directly affects glucose uptake and lipid metabolism. This notwithstanding, effects of GIP on other circulating metabolites than glucose have not been thoroughly investigated. Here, we examined effects of infusion of various concentrations of GIP in normo- and hyperglycemic rats on serum metabolite profiles. We found that, despite a decrease in serum glucose levels (-26%, p<0.01), the serum metabolite profile was largely unaffected by GIP infusion in normoglycemic rats. Interestingly, levels of branched chain amino acids and the ketone body β-hydroxybutyrate were decreased by 21% (p<0.05) and 27% (p<0.001), respectively, in hyperglycemic rats infused with 60 ng/ml GIP. Hence, our data suggest that GIP provokes a decrease in BCAA levels and ketone body production. Increased concentrations of these metabolites have been associated with obesity and T2D.
Protective effect of short-term treatment with parathyroid hormone 1-34 on oxidative stress is involved in insulin-like growth factor-I and nuclear factor erythroid 2-related factor 2 in rat bone marrow derived mesenchymal stem cells.
Oh YI, Kim JH, Kang CW
Regul Pept · 2014 Feb · PMID 24412273 · Publisher ↗
Bone marrow-derived mesenchymal stem cell (MSC)-mediated regeneration is a promising treatment for degenerative disease and traumatic injuries. MSCs can be isolated from rats using magnetic-activated cell sorting with CD...
Bone marrow-derived mesenchymal stem cell (MSC)-mediated regeneration is a promising treatment for degenerative disease and traumatic injuries. MSCs can be isolated from rats using magnetic-activated cell sorting with CD105 antibody. We investigated the relationships between the expression of endogenous insulin-like growth factor-I (IGF-I) and nuclear factor erythroid 2-related factor 2 (Nrf-2) during short-term treatment with parathyroid hormone (PTH) 1-34-induced protective response in MSCs. PTH 1-34 (10(-9)M) decreased reactive oxygen species (ROS) generation but increased cell viability and endogenous IGF-I (p<0.01). Suppression of IGF-I and Nrf-2 using specific small interfering RNA (siRNA) blocked the effects of PTH 1-34. Furthermore, increasing cell viability of PTH against hydrogen peroxide (H2O2) was suppressed by treatment with siRNA to IGF-I and Nr-2 (p<0.05). Exogenous IGF-I (10(-9)M) also increased endogenous IGF-I, cell viability, and Nrf-2 expression. These incremental increases were lessened by Nrf-2 siRNA (p<0.05). Exogenous IGF-I also inhibited the increase of H2O2-induced ROS generation, and the decrease of PTH 1-34-induced ROS generation in the presence of IGF-I and Nrf-2 siRNA. The increase of PTH 1-34-induced Nrf-2 expression was more significant in the nucleus than in the cytosol (p<0.05). PTH 1-34 also inhibited H2O2-induced inducible nitric oxide synthase expression, but increased the expression of heme oxygenase 1/2. The results implicate PTH 1-34, Nrf-2, and IGF-I signaling pathways in the response to oxidative stress. These factors could influence IGF-I regulation of metabolic fate and survival in MSCs.
Cardiac C-type natriuretic peptide gene expression and plasma concentrations in neonatal piglets.
Hansen LH, Smith J, Goetze JP
Regul Pept · 2014 Jan · PMID 24373811 · Publisher ↗
BACKGROUND: C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family. Cardiac ANP and BNP expressions are firmly established, whereas CNP expression in the mammalian heart remains controversial. In...
BACKGROUND: C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family. Cardiac ANP and BNP expressions are firmly established, whereas CNP expression in the mammalian heart remains controversial. In the present report, we used a porcine model of the neonatal period with high expressions of cardiac ANP and BNP in order to elucidate the cardiac CNP expression profile. METHODS: Plasma and cardiac tissue were obtained from newborn piglets during the first 72 h of life. The chamber-specific CNP mRNA contents were quantified by real-time PCR analysis. The proCNP concentrations in plasma and cardiac tissue extracts were quantified by a porcine-specific radioimmunoassay. RESULTS: Cardiac CNP mRNA contents (n=24) were low compared to sites of known expression, where porcine seminal vesicle CNP mRNA contents were 200-fold higher. In addition, plasma proCNP concentrations in the newborn piglets (n=44) were exceedingly low compared to proANP concentrations (5.3 pmol/L (3.2-8.6) vs. 3438 pmol/L (2790-5418), p<0.0001). The proCNP concentrations in atrial tissue extracts were barely detectable (≤0.06 pmol/g) (n=2) compared to ventricular proANP (130 pmol/g (101-159)) and atrial proANP (12,303 pmol/g (10,623-15,412)). CONCLUSION: Our data show that the heart is not a major source of circulating proCNP in neonatal piglets.
Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs.
Sigalet DL, de Heuvel E, Wallace L … +8 more , Bulloch E, Turner J, Wales PW, Nation P, Wizzard PR, Hartmann B, Assad M, Holst JJ
Regul Pept · 2014 Jan · PMID 24368164 · Publisher ↗
BACKGROUND: The enteroendocrine hormone glucagon like peptide-2 (GLP-2) and its ligands are under development as therapeutic agents for a variety of intestinal pathologies. A number of these conditions occur in neonates...
BACKGROUND: The enteroendocrine hormone glucagon like peptide-2 (GLP-2) and its ligands are under development as therapeutic agents for a variety of intestinal pathologies. A number of these conditions occur in neonates and infants, and thus a detailed understanding of the effects of GLP-2 during the phase of rapid growth during infancy is required to guide the development of therapeutic applications. We studied the effects of GLP-2 in the neonatal pig to determine the potential effects of exogenous administration. METHODS: Two day old newborn domestic piglets were treated with GLP-2 (1-33) at 40 μg/kg/day or control drug vehicle (saline), by subcutaneous injection, given in two doses per day, (n=6/group) for 42 days. Animals were weaned normally, over days 21-25. In the fifth week of life, they underwent neuro-developmental testing, and a pharmacokinetic study. On day 42, they were euthanized, and a complete necropsy performed, with histological assessment of tissues from all major organs. RESULTS: GLP-2 treatment was well tolerated, one control animal died from unrelated causes. There were no effects of GLP-2 on weight gain, feed intake, or behavior. In the treated animals, GLP-2 levels were significantly elevated at 2400±600 pM while at necropsy, organ weights and histology were not affected except in the intestine, where the villus height in the small intestine and the crypt depth, throughout the small intestine and colon, were increased. Similarly, the rate of crypt cell proliferation (Ki-67 staining) was increased in the GLP-2 treated animals and the rate of apoptosis (Caspase-3) was decreased, the depth of the microvilli was increased and the expression of the mRNA for the GLP-2 receptor was decreased throughout the small and large intestine. CONCLUSIONS: In these growing animals, exogenous GLP-2 at pharmacologic doses was well tolerated, with effects confined to the gastrointestinal tract.
Unexpected effects of voluntary exercise training on natriuretic peptide and receptor mRNA expression in the ob/ob mouse heart.
Broderick TL, Wang D, Jankowski M … +1 more , Gutkowska J
Regul Pept · 2014 Jan · PMID 24365091 · Publisher ↗
Regular exercise is generally recommended for the treatment of obesity and type 2 diabetes. Exercise reduces body weight, improves glycemic control and cardiovascular (CV) function. This study was designed to determine t...
Regular exercise is generally recommended for the treatment of obesity and type 2 diabetes. Exercise reduces body weight, improves glycemic control and cardiovascular (CV) function. This study was designed to determine the impact of voluntary wheel running on the cardiac oxytocin (OT)-natriuretic peptide (NP) system and plasma CV risk factors in the ob/ob mouse, a model of insulin resistance coupled with severe obesity. Five-week-old male ob/ob mice and non-obese heterozygote control littermates were assigned to either a sedentary or running group. Voluntary running was performed using a wheel system for a period of 8 weeks. Compared to non-obese mice, daily running activity expressed in kilometers, was significantly lower in ob/ob mice. In these mice, voluntary running improved body weight, but exacerbated CV markers, including plasma glucose and triglyceride levels. OT receptor gene expression was decreased in hearts of ob/ob mice compared to non-obese mice, and no improvement in the expression of this receptor was observed after voluntary running. Hearts from ob/ob mice also expressed lower BNP mRNA, whereas no differences in A- and C-type NP were observed between non-obese and ob/ob mice. After voluntary running, a downregulation in the expression of all three NPs coupled with increased apoptosis was observed in ob/ob hearts. Our results show that voluntary exercise running activity was decreased in the ob/ob mouse. Surprisingly, this was associated with a worsening of common CV plasma markers, reduced expression of peptides linked to the cardioprotective OT-NP system, and increased expression of cardiac apoptotic markers.
The inhibitory effect of anandamide on oxytocin and vasopressin secretion from neurohypophysis is mediated by nitric oxide.
Luce V, Fernandez Solari J, Rettori V … +1 more , De Laurentiis A
Regul Pept · 2014 Jan · PMID 24342802 · Publisher ↗
The neurohypophyseal hormones oxytocin (OT) and vasopressin (VP) are involved in behavioral, autonomic and neuroendocrine functions. Both peptides are synthesized in magnocellular neurons of paraventricular and supraopti...
The neurohypophyseal hormones oxytocin (OT) and vasopressin (VP) are involved in behavioral, autonomic and neuroendocrine functions. Both peptides are synthesized in magnocellular neurons of paraventricular and supraoptic nuclei at hypothalamic level whose axons terminate in the neurohypophysis (NH), from where OT and VP are released into the systemic circulation. NH contains abundant nitric oxide (NO) synthase suggesting that NO plays a role in the release of these neuropeptides. The endocannabinoid system is present in magnocellular neurons of the hypothalamic neurohypophyseal system, and we have previously demonstrated that endocannabinoids modulate OT secretion at hypothalamic level. In the present work, we investigated the in vitro effect of the endocannabinoid anandamide (AEA) on OT and VP release from NH of untreated adult male rats and the involvement of NO in this action. Our results showed that AEA decreased OT and VP secretion from NH. AEA action was mediated by NO, since the inhibition of NO synthesis completely blocked this inhibitory effect. We found that cannabinoid receptor type 2 (CB2) and transient receptor potential cation channel subfamily V member 1 (TRPV1) are involved in the inhibitory effect of AEA because AM630 and capsazepine, CB2 and TRPV1 antagonists respectively, but not AM251, a CB1 antagonist, blocked AEA effect at neurohypophyseal level. These findings revealed an interaction between endocannabinoid, nitric oxide and oxytocin/vasopressin systems that could be involved in the modulation of homeostatic, behavioral and reproductive processes.
Nesfatin-1 in childhood and adolescent obesity and its association with food intake, body composition and insulin resistance.
Anwar GM, Yamamah G, Ibrahim A … +3 more , El-Lebedy D, Farid TM, Mahmoud R
Regul Pept · 2014 Jan · PMID 24333832 · Publisher ↗
Nesfatin-1 is an anorexigenic peptide that controls feeding behavior and glucose homeostasis. However, there is little data that exists regarding nesfatin-1 secretion in obese children and young adolescents. The aim of t...
Nesfatin-1 is an anorexigenic peptide that controls feeding behavior and glucose homeostasis. However, there is little data that exists regarding nesfatin-1 secretion in obese children and young adolescents. The aim of this study is to investigate serum nesfatin-1 in childhood and adolescent obesity and to study potential correlations with food intake, anthropometric indices, body composition and insulin resistance. Forty obese children and adolescents and 40 healthy control subjects were studied. Anthropometric measurements were assessed, dietary food intake was evaluated based on 3-days food record and body composition indices were evaluated using bioelectrical impedance analysis. Lipid profile, fasting blood sugar, fasting insulin and HOMA-IR were measured. Fasting serum nesfatin-1 was quantitatively assayed by ELISA. Serum nesfatin-1 was significantly higher in obese group (2.49±1.96 ng/ml) than in control group (0.70±0.81 ng/ml), P=0.001. Positive correlations with serum insulin (P=0.001), HOMA-IR (P=0.000), BMI-SDS (P=0.04), body fat % (P=0.000), fat mass (P=0.000), fat free mass (P=0.03), CHO % (P=0.000), and saturated fat % (P=0.01) were found. While significant negative correlation with protein % (P=0.000) was observed. In conclusion, our results denote that nesfatin-1 might have an important role in regulation of food intake and pathogenesis of insulin resistance in obese children and young adolescents.
Des-aspartate-angiotensin I attenuates ICAM-1 formation in hydrogen peroxide-treated L6 skeletal muscle cells and soleus muscle of mice subjected to eccentric exercise.
Sim MK, Wong YC, Xu XG … +1 more , Loke WK
Regul Pept · 2014 Jan · PMID 24333630 · Publisher ↗
L6 skeletal muscle cells overexpressed ICAM-1 when treated with H2O2. Maximum effect was observed at 200 μM H2O2. Des-aspartate-angiotensin I (DAA-I) concentration-dependently attenuated the overexpression. Maximum atten...
L6 skeletal muscle cells overexpressed ICAM-1 when treated with H2O2. Maximum effect was observed at 200 μM H2O2. Des-aspartate-angiotensin I (DAA-I) concentration-dependently attenuated the overexpression. Maximum attenuation occurred at 10(-10) M DAA-I. H2O2 activated NFκB and its translocation into the nucleus of L6 muscle cells suggesting that NFκB mediates the H2O2-induced overexpression of ICAM-1. DAA-I inhibited the activation and translocation of NFκB. H2O2 is a major oxidant formed during skeletal muscle contraction and is implicated in oxidative stress and skeletal muscle damage in excessive unaccustomed exercise. The data show that DAA-I has antioxidant action, and its action was further investigated in the soleus muscle of mice subjected to 240 min of eccentric exercise on a rodent treadmill. The eccentric exercise induced superoxide formation and overexpression of ICAM-1 in the soleus muscle of the mice at 3 days post exercise. DAA-I (0.2 nmole/kg/day) administered orally on day 1 (pre-exercise) and 2 days post-exercise attenuated both the ROS formation and ICAM-1 overexpression. Earlier studies show that DAA-I acts as an agonist on the angiotensin AT1 receptor and elicits responses opposing those of angiotensin II. The present and earlier findings support the recent suggestion that angiotensin II is involved in skeletal muscle damage, and curtailment of its actions via ACE inhibitors and losartan protects and improves skeletal muscle damage. These findings open up new avenues for treatment and management of skeletal muscle damage via the interventions of the renin angiotensin system.
Orexin A and B in vitro modify orexins receptors expression and gonadotropins secretion of anterior pituitary cells of proestrous rats.
Cataldi NI, Lux Lantos VA, Libertun C
Regul Pept · 2014 Jan · PMID 24333629 · Publisher ↗
AIM: Orexin A and orexin B (hypocretins) are neuropeptides synthesized mainly by neurons located in the lateral hypothalamus and projections throughout the brain. They are agonists at both the orexin 1 and orexin 2G prot...
AIM: Orexin A and orexin B (hypocretins) are neuropeptides synthesized mainly by neurons located in the lateral hypothalamus and projections throughout the brain. They are agonists at both the orexin 1 and orexin 2G protein-coupled receptors. They have been related to arousal, sleep and feeding, autonomic and neuroendocrine functions. Their role in the brain control of gonadotropins secretion was postulated in rodents and humans. Previously, we demonstrated the participation of the orexinergic system in attaining successful reproduction in in vivo studies. METHODS: We studied in vitro the effects of both neuropeptides, in the presence or absence of selective antagonists, on the mRNA expression of orexin 1 and orexin 2 receptors in anterior pituitary cells of proestrous rats, as well as the direct effects on FSH and LH secretion. RESULTS: Both orexin A and orexin B increased FSH and LH secretion; these effects were suppressed by the orexin 1 receptor blocking agent SB-334867 and the orexin 2 receptor antagonists JNJ-10397049. Orexin A and orexin B decreased OX1 receptor mRNA expression and this effect was modified only when both blocking agents were present. Neither orexin A nor the blocking drugs by themselves modified OX2 receptor mRNA expression. Orexin B treatment increased the mRNA expression of OX2 receptor. The effect was abolished only by the OX2 receptor antagonist. CONCLUSION: In an in vitro model, we demonstrated a direct effect of orexins on gonadotropins release and orexins receptors expression, underlining the hypothesis that orexins participate in the brain control of pituitary functions.
The actions of neuropeptide SF on the hypothalamic-pituitary-adrenal axis and behavior in rats.
Jászberényi M, Bagosi Z, Csabafi K … +2 more , Palotai M, Telegdy G
Regul Pept · 2014 Jan · PMID 24316399 · Publisher ↗
Present experiments focused on measuring the effect of neuropeptide SF (NPSF) on the hypothalamus-pituitary-adrenal (HPA) axis and behavior. The peptide was administered in different doses (0.25, 0.5, 1, 2 μg) intracereb...
Present experiments focused on measuring the effect of neuropeptide SF (NPSF) on the hypothalamus-pituitary-adrenal (HPA) axis and behavior. The peptide was administered in different doses (0.25, 0.5, 1, 2 μg) intracerebroventricularly to rats, and the behavior of which was then observed by telemetry and open-field test. Effect of NPSF on core temperature was also measured via telemetry. Plasma ACTH and corticosterone concentrations were measured to assess the influence of NPSF on the HPA activation. In addition, the changes in corticotrophin-releasing hormone (CRH) level in the hypothalamic paraventricular nucleus were continuously monitored by means of intracerebral microdialysis. Our results showed that NPSF augmented paraventricular CRH release and increased ACTH and corticosterone levels in the plasma. The release of corticosterone was successfully blocked by the pre-treatment of the CRH antagonist α-helical CRH9-41. Spontaneous and exploratory locomotor activity was also stimulated according to the telemetric and open-field studies. However, NPSF only tended to alter stereotyped behavior in the open-field experiments. These results demonstrate that NPSF may play a physiologic role in the regulation of such circadian functions as the activity of motor centers and the HPA axis, through the release of CRH.
Abnormal rectal endocrine cells in patients with irritable bowel syndrome.
El-Salhy M, Gundersen D, Hatlebakk JG … +2 more , Gilja OH, Hausken T
Regul Pept · 2014 Jan · PMID 24316398 · Publisher ↗
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. In a previous study the total number of endocrine cells in the rectum of IBS patients, as detected by chromogranin A, did not differ from that of heal...
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. In a previous study the total number of endocrine cells in the rectum of IBS patients, as detected by chromogranin A, did not differ from that of healthy controls. While the total endocrine cell content of the rectum appears to be unchanged in IBS patients, changes in particular endocrine cells cannot be excluded. This study was undertaken, therefore, to investigate the cell density of different rectal endocrine cell types in (IBS) patients. Fifty patients with IBS (41 females and 9 males) were included in the study. Thirty patients had diarrhoea (IBS-D) and 20 had constipation (IBS-C) as the predominant symptom. Twenty-seven subjects were included as controls (19 females and 8 males). Rectal biopsy specimens were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), and oxyntomodulin and somatostatin cells. The cell densities were quantified by computerised image analysis. The serotonin cell density did not differ significantly, although a type II statistical error cannot be excluded, due to the small size of the sample. The densities of PYY and Oxyntomodulin cells were significantly lower and that of somatostatin were significantly higher in IBS patients than controls. These abnormalities were observed in both IBS-D and IBS-C patients. The abnormalities in the endocrine cells observed in this study in the rectum differed considerably from those seen in the colon of IBS patients. This indicates that caution in using the rectum to represent the large intestine in these patients. These abnormalities could be primary (genetic) or secondary to changes in the gut hormones found in other segments of the gut and/or other pathological processes. Although the-cause-and effect relationship of the abnormalities found in rectal endocrine cells is difficult to elucidate, they might contribute to the symptoms associated with IBS. The densities of PYY and somatostatin cells are potential biomarkers with good sensitivity and specificity for the diagnosis of IBS.
Octreotide modulates the effects on fibrosis of TNF-α, TGF-β and PDGF in activated rat hepatic stellate cells.
Klironomos S, Notas G, Sfakianaki O … +3 more , Kiagiadaki F, Xidakis C, Kouroumalis E
Regul Pept · 2014 Jan · PMID 24291170 · Publisher ↗
BACKGROUND AND AIMS: Somatostatin and its analogs may influence hepatic fibrosis interfering through several mechanisms. The aim of this study was to investigate the effect of octreotide on cytokine activated hepatic ste...
BACKGROUND AND AIMS: Somatostatin and its analogs may influence hepatic fibrosis interfering through several mechanisms. The aim of this study was to investigate the effect of octreotide on cytokine activated hepatic stellate cells (HSC). METHODS: Primary HSCs were isolated from rats and were cultured on plastic for activation. Expression of somatostatin receptors (SSTR) was investigated in cultured HSCs by immunofluorescence and western blot. The effect of octreotide on cellular proliferation was studied with the MTT assay and western blot for α1-procollagen (α1-PROC) production in TNFα, TGF-β1 or PDGF treated HSCs. Phosphotyrosine (PTP) and phosphoserine-phosphothreonine (STP) phosphatases inhibition was performed with sodium orthovanadate and okadaic acid respectively. RESULTS: Activated HSC express SSTR subtypes 1, 2A, 2B, 3 and 4 and their expression is enhanced by further HSC activation. Octreotide did not have an effect on HSC proliferation but inhibited plastic induced α1-PROC production. Interestingly, it enhanced PDGF-induced HSC proliferation but inhibited PDGF and TGFβ1 dependent expression of α1-PROC, while an opposite effect was observed in TNFα-induced cell proliferation and collagen production. PTP inhibition reversed the inhibitory effect of octreotide on α1-PROC, but potentiated its effect on PDGF and TGFβ1 dependent α1-PROC production. Finally, STP inhibition profoundly inhibited α1-PROC expression in all cases suggesting that both STP and PTP phosphatases are important regulators of pro-fibrotic mechanisms. CONCLUSIONS: The net effect of octreotide on HSCs and therefore liver fibrosis is subject to the cytokine microenvironment of these cells. This effect is modulated by PTPs and STPs inhibition. Especially in the case of STPs their profibrotic effects could be an interesting new therapeutic target in liver fibrosis.
Neuropeptide Y regulates the leptin receptors in rat hypothalamic and pituitary explant cultures.
Di Yorio MP, Bilbao MG, Faletti AG
Regul Pept · 2014 Jan · PMID 24291064 · Publisher ↗
The aim of this work was to investigate whether the expression of leptin receptors (OBR) in the hypothalamic-pituitary (HP) axis is regulated by the orexigenic neuropeptide Y (NPY) during ovulation. To this end, we perfo...
The aim of this work was to investigate whether the expression of leptin receptors (OBR) in the hypothalamic-pituitary (HP) axis is regulated by the orexigenic neuropeptide Y (NPY) during ovulation. To this end, we performed in vitro assays, using cultures of both hypothalamic and anterior pituitary explants from immature rats primed with gonadotropins to induce ovulation. In hypothalamic explants, protein expression of both the long and short OBR isoforms was increased by the presence of NPY at 100-500 ng/ml and at 300-500 ng/ml, respectively. Similarly, in pituitary explants, protein expression of the long isoform was increased between 30 and 300 ng/ml while that of the short isoform was increased only at 300 ng/ml. When both tissues were incubated with NPY and BIBP3226, a specific antagonist of the NPY Y1 receptor subtype, the NPY-induced protein expression was totally reversed by the antagonist at almost every concentration assayed. However, this antagonist was not always capable of blocking the increase caused by the presence of NPY at transcript level. In conclusion, our results indicate that NPY is able to regulate the expression of both the long and the short isoforms of OBR in the HP axis, at least in part, through the NPY Y1 receptor. These results reinforce the fact that NPY and its NPY Y1 receptor play a critical role in reproduction by modulating leptin sensitivity.
Corticotropin-releasing factor-like peptide modifies the AMPA-, NMDA-dependent and GABAB-ergic properties of synaptic transmissions in vitro.
Mokrushin AA
Regul Pept · 2014 Jan · PMID 24275468 · Publisher ↗
The aim of this study was to investigate the neurotrophic effects of the mystixin-7 mini-peptide (MTX, a synthetic corticotrophin-releasing-factor-like peptide-like peptide) using a slice-based system. The technique on-l...
The aim of this study was to investigate the neurotrophic effects of the mystixin-7 mini-peptide (MTX, a synthetic corticotrophin-releasing-factor-like peptide-like peptide) using a slice-based system. The technique on-line monitoring of electrophysiological parameters (excitatory glutamatergic AMPAR-, NMDAR-dependent and inhibitory GABAB-ergic postsynaptic mechanisms) in the olfactory cortex slices of the rat brain exposed to varied amounts of MTX was used. MTX in a dose-dependent manner inhibited both the AMPAR- and NMDAR-mediated postsynaptic processes. The peptide caused depression of inhibitory GABAB-ergic processes only at low doses of MTX (10, 25, 50 mg/mL) while at higher doses (100, 250 mg/mL) it enhanced them. These effects of MTX were reversible. AMPA-dependent (but not NMDA-mediated mechanisms) and inhibitory processes were restored after washing. Triple reperfusion of slices with MTX (100 mg/mL) accelerated the inhibitory processes and induced NMDAR desensitization. MTX evoked the long-term depression on θ burst stimulation of the slices. This study did not only lead to the conclusion that the functions of the MTX mini-peptide is not limited to anti-inflammatory effects, but also is included modifications of excitatory glutamatergic AMPAR-, NMDAR-dependent and inhibitory GABAB-ergic postsynaptic mechanisms.
Evaluation of somatostatin receptor subtype expression in human neuroendocrine tumors using two sets of new monoclonal antibodies.
Lambertini C, Barzaghi-Rinaudo P, D'Amato L … +3 more , Schulz S, Nuciforo P, Schmid HA
Regul Pept · 2013 Nov · PMID 24188818 · Publisher ↗
INTRODUCTION: The expression and reliable detection of somatostatin receptor subtypes (SSTR1-5) is a prerequisite for the successful use of somatostatin analogs in neuroendocrine tumors (NETs). Two sets of monoclonal ant...
INTRODUCTION: The expression and reliable detection of somatostatin receptor subtypes (SSTR1-5) is a prerequisite for the successful use of somatostatin analogs in neuroendocrine tumors (NETs). Two sets of monoclonal antibodies (mAbs) against human SSTR1, 2A, 3 and 5 have recently been developed by two independent laboratories using rabbit and mouse hybridomas. Our aim was to evaluate the usefulness of both sets of mAbs for detection of SSTRs in NET samples as they are routinely collected in clinical practice. METHODS: Mouse and rabbit mAbs were characterized in SSTR1, 2A, 3 and 5-transfected HEK293 cells and human archival samples of pancreatic tissue and NET. Comparative analysis of mAbs was also conducted by immunostaining of a tissue microarray composed of 75 cores of NET. RESULTS: Immunohistochemical analysis of HEK293 cells showed that both rabbit and mouse mAbs specifically detect their cognate receptor subtype, with mild cytoplasmic cross-reactivity observed for rabbit mAbs. Both sets of mAbs labeled normal pancreatic islets and showed similar patterns of immunoreactivity in NET controls. Direct comparison of mAb sets using a NET tissue microarray revealed strong correlation between rabbit and mouse mAbs against SSTR1 and 5, and moderate correlation for SSTR3. The rabbit mAb against SSTR2A showed higher affinity for its cognate receptor than the corresponding mouse mAb, resulting in a more reliable detection of this SSTR. CONCLUSIONS: mAbs from both sets are reliable tools for the detection of SSTR1, 3 and 5, whereas the rabbit mAb against SSTR2A is recommended for use in routine clinical testing due to its superior binding affinity.
Anti-tumor activities of the host-defense peptide hymenochirin-1B.
Attoub S, Arafat H, Mechkarska M … +1 more , Conlon JM
Regul Pept · 2013 Nov · PMID 24185042 · Publisher ↗
The hymenochirins are a family of cationic, amphipathic, α-helical host-defense peptides, first isolated from skin secretions of the Congo clawed frog Hymenochirus boettgeri (Pipidae). Of the four hymenochirins tested, h...
The hymenochirins are a family of cationic, amphipathic, α-helical host-defense peptides, first isolated from skin secretions of the Congo clawed frog Hymenochirus boettgeri (Pipidae). Of the four hymenochirins tested, hymenochirin-1B (IKLSPETKDNLKKVLKGAIKGAIVAKMV.NH2) shows the greatest cytotoxic potency against non-small cell lung adenocarcinoma A549 cells (LC50=2.5±0.2 μM), breast adenocarcinoma MDA-MB-231 cells (LC50=9.0±0.3 μM), colorectal adenocarcinoma HT-29 cells (LC50=9.7±0.2 μM), and hepatocarcinoma HepG2 cells (LC50=22.5±1.4 μM) with appreciably less hemolytic activity against human erythrocytes (LC50=213±18μM). Structure-activity relationships were investigated by synthesizing analogs of hymenochirin-1B in which Pro(5), Glu(6) and Asp(9)on the hydrophilic face of the helix were replaced by one or more L-lysine or D-lysine residues. The [D9K] analog displays the greatest increase in potency against all four cell lines (up to 6 fold) but hemolytic activity also increases (LC50=174±12 μM). The [D9k] and [E6k,D9k] analogs retain relatively high cytotoxic potency against the tumor cells (LC50 in the range 2.1-21 μM) but show reduced hemolytic activity (LC50>300 μM). The data suggest that hymenochirin-1B has therapeutic potential as a template to generate potent, non-toxic anti-cancer agents.
Arginine vasopressin, via activation of post-junctional V1 receptors, induces contractile effects in mouse distal colon.
Mastropaolo M, Zizzo MG, Auteri M … +2 more , Mulè F, Serio R
Regul Pept · 2013 Nov · PMID 24185041 · Publisher ↗
The aim of this study was to analyze whether arginine vasopressin (AVP) may be considered a modulator of intestinal motility. In this view, we evaluated, in vitro, the effects induced by exogenous administration of AVP o...
The aim of this study was to analyze whether arginine vasopressin (AVP) may be considered a modulator of intestinal motility. In this view, we evaluated, in vitro, the effects induced by exogenous administration of AVP on the contractility of mouse distal colon, the subtype(s) of receptor(s) activated and the action mechanism. Isometric recordings were performed on longitudinal and circular muscle strips of mouse distal colon. AVP (0.001 nM-100 nM) caused concentration-dependent contractile effects only on the longitudinal muscle, antagonized by the V1 receptor antagonist, V-1880. AVP-induced effect was not modified by tetrodotoxin, atropine and indomethacin. Contractile response to AVP was reduced in Ca(2+)-free solution or in the presence of nifedipine, and it was abolished by depletion of calcium intracellular stores after repetitive addition of carbachol in calcium-free medium with addition of cyclopiazonic acid. U-73122, an inhibitor of the phospholipase C, effectively antagonized AVP effects, whilst it was not affected by an adenylyl cyclase inhibitor. Oxytocin induced an excitatory effect in the longitudinal muscle of distal colon at very high concentrations, effect antagonized by V-1880. The results of this study shown that AVP, via activation of V1 receptors, is able to modulate positively contractile activity of longitudinal muscle of mouse distal colon, independently by enteric nerve activation and prostaglandin synthesis. Contractile response is achieved by increase in cytoplasmatic Ca(2+) concentration via extracellular Ca(2+) influx from L-type Ca(2+) channels and via Ca(2+) release from intracellular stores through phospholipase C pathway. No modulation has been observed on the contractility of the circular muscle.
Central administration of mesotocin inhibits feeding behavior in chicks.
Masunari K, Khan MS, Cline MA … +1 more , Tachibana T
Regul Pept · 2013 Nov · PMID 24183984 · Publisher ↗
Mesotocin (MT) is a neurohypophysis hormone in non-mammalian vertebrates including chickens, and homologous of oxytocin (OT) in mammals. Oxytocin (OT) is a well known reproductive hormone in mammals, but the physiologica...
Mesotocin (MT) is a neurohypophysis hormone in non-mammalian vertebrates including chickens, and homologous of oxytocin (OT) in mammals. Oxytocin (OT) is a well known reproductive hormone in mammals, but the physiological roles of MT in chickens have not been clarified well. OT is thought to regulate feeding behavior because central and peripheral injections of OT inhibit feeding behavior in mammals. In avian, on the other hand, the effect of MT on feeding regulation has not yet been clarified. Therefore, the present study was carried out to examine whether MT is related to the regulation of feeding in chicks (Gallus gallus). Intracerebroventricular (ICV) injection of MT significantly decreased food intake in chicks while intraperitoneal injection had no effect. Behavioral observations revealed that ICV injection of MT significantly increased wing-flapping and preening, and tended to increase voluntary movement, implying that the anorexigenic effect of MT might be related to the stress response. However, neither plasma corticosterone concentration nor the mRNA expression of corticotrophin-releasing hormone (CRH) in the diencephalon was affected by ICV injection of MT. Moreover; ICV injection of CRH did not affect MT mRNA expression in the diencephalon. In sum, central injection of MT is associated with an anorexigenic response that does not appear CRH dependent in chicks.
The combination of GIP plus xenin-25 indirectly increases pancreatic polypeptide release in humans with and without type 2 diabetes mellitus.
Chowdhury S, Wang S, Patterson BW … +2 more , Reeds DN, Wice BM
Regul Pept · 2013 Nov · PMID 24183983 · Full text
Xenin-25 (Xen) is a 25-amino acid neurotensin-related peptide that activates neurotensin receptor-1 (NTSR1). We previously showed that Xen increases the effect of glucose-dependent insulinotropic polypeptide (GIP) on ins...
Xenin-25 (Xen) is a 25-amino acid neurotensin-related peptide that activates neurotensin receptor-1 (NTSR1). We previously showed that Xen increases the effect of glucose-dependent insulinotropic polypeptide (GIP) on insulin release 1) in hyperglycemic mice via a cholinergic relay in the periphery independent from the central nervous system and 2) in humans with normal or impaired glucose tolerance, but not type 2 diabetes mellitus (T2DM). Since this blunted response to Xen defines a novel defect in T2DM, it is important to understand how Xen regulates islet physiology. On separate visits, subjects received intravenous graded glucose infusions with vehicle, GIP, Xen, or GIP plus Xen. The pancreatic polypeptide response was used as an indirect measure of cholinergic input to islets. The graded glucose infusion itself had little effect on the pancreatic polypeptide response whereas administration of Xen equally increased the pancreatic polypeptide response in humans with normal glucose tolerance, impaired glucose tolerance, and T2DM. The pancreatic polypeptide response to Xen was similarly amplified by GIP in all 3 groups. Antibody staining of human pancreas showed that NTSR1 is not detectable on islet endocrine cells, sympathetic neurons, blood vessels, or endothelial cells but is expressed at high levels on PGP9.5-positive axons in the exocrine tissue and at low levels on ductal epithelial cells. PGP9.5 positive nerve fibers contacting beta cells in the islet periphery were also observed. Thus, a neural relay, potentially involving muscarinic acetylcholine receptors, indirectly increases the effects of Xen on pancreatic polypeptide release in humans.
Gastric distension activates NUCB2/nesfatin-1-expressing neurons in the nucleus of the solitary tract.
Bonnet MS, Ouelaa W, Tillement V … +7 more , Trouslard J, Jean A, Gonzalez BJ, Gourcerol G, Dallaporta M, Troadec JD, Mounien L
Regul Pept · 2013 Nov · PMID 24120633 · Publisher ↗
Brainstem structures such as the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMNX) are essential for the digestive function of the stomach. A large number of neurotransmitters inc...
Brainstem structures such as the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMNX) are essential for the digestive function of the stomach. A large number of neurotransmitters including glutamate and gamma-aminobutyric acid (GABA) are involved in the central control of gastric functions. However, the neuropeptidergic systems implicated in this process remain undetermined. Nesfatin-1 was recently identified as a neuropeptide cleaved from the N-terminal part of NEFA/nucleobindin 2 precursor (NUCB2). Central administration of this neuropeptide inhibits food consumption and gastroduodenal motility in rodents. Interestingly, the NTS and the DMNX contain a dense population of NUCB2/nesfatin-1 cell bodies. These observations led us to investigate the possible involvement of NUCB2/nesfatin-1 neurons in the brainstem neuronal pathways that modulate gastric functions. We observed an activation of NTS NUCB2/nesfatinergic neurons after gastric distention in rats. In addition, we found that several NTS NUCB2/nesfatinergic neurons were GABAergic. Finally, when fluorogold was injected at the stomach level, many retrogradely labeled neurons were observed in the DMNX which were also positive for NUCB2/nesfatin-1. Taken together, these observations suggest for the first time that NUCB2/nesfatin-1 neurons of the NTS are sensitive to gastric distension and then may contribute to the satiety signal.
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