scholarly journals Molecular Characterization and Biological Function of Neuroendocrine Regulatory Peptide-3 in the Rat

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1377-1386 ◽  
Author(s):  
Hiroaki Fujihara ◽  
Kazuki Sasaki ◽  
Emi Mishiro-Sato ◽  
Toyoaki Ohbuchi ◽  
Govindan Dayanithi ◽  
...  

Neuroendocrine regulatory peptide (NERP)-3, derived from the neurosecretory protein VGF (non-aconymic), is a new biologically active peptide identified through peptidomic analysis of the peptides secreted by an endocrine cell line. Using a specific antibody recognizing the C-terminal region of NERP-3, immunoreactive (ir)-NERP-3 was identified in acid extracts of rat brain and gut as a 30-residue NERP-3 with N-terminal pyroglutamylation. Assessed by radioimmunoassay, ir-NERP-3 was more abundant in the brain, including the posterior pituitary (PP), than in the gut. Immunohistochemistry demonstrated that ir-NERP-3 was significantly increased in the suprachiasmatic nucleus, the magnocellular division of the paraventricular nucleus, and the external layer of the median eminence, but not in the supraoptic nucleus, after dehydration. The immunoreactivity was, however, markedly decreased in all of these locations after chronic salt loading. Intracerebroventricular administration of NERP-3 in conscious rats induced Fos expression in a subset of arginine vasopressin (AVP)-containing neurons in the supraoptic nucleus and the magnocellular division of the paraventricular nucleus. On in vitro isolated rat PP preparations, NERP-3 caused a significant AVP release in a dose-related manner, suggesting that NERP-3 in the PP could be an autocrine activator of AVP release. Taken together, the present results suggest that NERP-3 in the hypothalamo-neurohypophyseal system may be involved in the regulation of body fluid balance.

2007 ◽  
Vol 35 (5) ◽  
pp. 1252-1257 ◽  
Author(s):  
I.D. Neumann

The brain oxytocin system has served as a distinguished model system in neuroendocrinology to study detailed mechanisms of intracerebral release, in particular of somatodendritic release, and its behavioural and neuroendocrine consequences. It has been shown that oxytocin is released within various brain regions, but evidence for dendritic release is limited to the main sites of oxytocin synthesis, i.e. the hypothalamic SON (supraoptic nucleus) and PVN (paraventricular nucleus). In the present paper, stimuli of dendritic release of oxytocin and the related neuropeptide vasopressin are discussed, including parturition and suckling, i.e. the period of a highly activated brain oxytocin system. Also, exposure to various pharmacological, psychological or physical stressors triggers dendritic oxytocin release, as monitored by intracerebral microdialysis within the SON and PVN during ongoing behavioural testing. So far, dendritic release of the neuropeptide has only been demonstrated within the hypothalamus, but intracerebral oxytocin release has also been found within the central amygdala and the septum in response to various stimuli including stressor exposure. Such a locally released oxytocin modulates physiological and behavioural reproductive functions, emotionality and hormonal stress responses, as it exerts, for example, pro-social, anxiolytic and antistress actions within restricted brain regions. These discoveries make oxytocin a promising neuromodulator of the brain for psychotherapeutic intervention and treatment of numerous psychiatric illnesses, for example, anxiety-related diseases, social phobia, autism and postpartum depression.


1991 ◽  
Vol 9 (2) ◽  
pp. 169-172
Author(s):  
Seiji Koide ◽  
Hiroshi Onishi ◽  
Masafumi Katayama ◽  
Sakae Yamagami ◽  
Yukio Kawakita

2006 ◽  
Vol 72 (2) ◽  
pp. 1459-1466 ◽  
Author(s):  
Philip A. Wescombe ◽  
Mathew Upton ◽  
Karen P. Dierksen ◽  
Nancy L. Ragland ◽  
Senthuran Sivabalan ◽  
...  

ABSTRACT Salivaricin A (SalA), the first Streptococcus salivarius lantibiotic to be characterized, appears to be inhibitory to most Streptococcus pyogenes strains. A variant of the SalA structural gene (salA1) is present in more than 90% of S. pyogenes strains, but only strains of M serotype 4 and T pattern 4 produce the biologically active peptide. The present study identifies four additional variants (salA2 to salA5) of the SalA structural gene and demonstrates that each of the corresponding inhibitory peptides (SalA2 to SalA5) is produced in vitro. These variants appear to be similar to SalA and SalA1 in their inhibitory activity against Micrococcus luteus and in their ability to act as inducers of SalA production. It had previously been shown that S. pyogenes strain SF370 had a deletion (of approximately 2.5 kb) in the salM and salT genes of the salA1 locus. In the present study, several additional characteristic deletions within the salA1 loci were identified. S. pyogenes strains of the same M serotype all share the same salA1 locus structure. Since S. salivarius is a predominant member of the normal oral flora of healthy humans, strains producing anti-S. pyogenes lantibiotics, such as SalA, may have excellent potential for use as oral probiotics. In the present study, we have used a highly specific SalA induction system to directly detect the presence of SalA in the saliva of humans who either naturally harbor populations of SalA-producing S. salivarius or who have been colonized with the SalA2-producing probiotic S. salivarius K12.


2015 ◽  
Vol 308 (7) ◽  
pp. R559-R568 ◽  
Author(s):  
Michael P. Greenwood ◽  
Andre S. Mecawi ◽  
See Ziau Hoe ◽  
Mohd Rais Mustafa ◽  
Kory R. Johnson ◽  
...  

Salt loading (SL) and water deprivation (WD) are experimental challenges that are often used to study the osmotic circuitry of the brain. Central to this circuit is the supraoptic nucleus (SON) of the hypothalamus, which is responsible for the biosynthesis of the hormones, arginine vasopressin (AVP) and oxytocin (OXT), and their transport to terminals that reside in the posterior lobe of the pituitary. On osmotic challenge evoked by a change in blood volume or osmolality, the SON undergoes a function-related plasticity that creates an environment that allows for an appropriate hormone response. Here, we have described the impact of SL and WD compared with euhydrated (EU) controls in terms of drinking and eating behavior, body weight, and recorded physiological data including circulating hormone data and plasma and urine osmolality. We have also used microarrays to profile the transcriptome of the SON following SL and remined data from the SON that describes the transcriptome response to WD. From a list of 2,783 commonly regulated transcripts, we selected 20 genes for validation by qPCR. All of the 9 genes that have already been described as expressed or regulated in the SON by osmotic stimuli were confirmed in our models. Of the 11 novel genes, 5 were successfully validated while 6 were false discoveries.


1986 ◽  
Vol 369 (1-2) ◽  
pp. 37-47 ◽  
Author(s):  
Kiyotoshi Inenaga ◽  
Richard E.J. Dyball ◽  
Shiguru Okuya ◽  
Hiroshi Yamashita

2020 ◽  
Author(s):  
Aminata P. Coulibaly ◽  
Pinar Pezuk ◽  
Paul Varghese ◽  
William Gartman ◽  
Danielle Triebwasser ◽  
...  

Abstract Background: Aneurysmal subarachnoid hemorrhage (SAH) is associated with the development of delayed cognitive deficits. Neutrophil infiltration into the central nervous system (CNS) is linked to the development of these deficits after SAH. It is however unclear how neutrophil activity influences CNS function in SAH. As such, the present project aims to elucidate neutrophil factors and mechanisms mediating CNS injury and cognitive deficits after SAH. Methods: Using a murine model of SAH and mice deficient in neutrophil effector functions, we determined which neutrophil effector function is critical to the development of deficits after SAH. Also, in vitro techniques were used to elucidate how neutrophils affect cellular function of neurons and glia after SAH. Results: Our results show that following SAH, neutrophils infiltrate the meninges, and not the brain parenchyma. Mice lacking functional myeloperoxidase (MPO KO), a neutrophil enzyme, lack both the meningeal neutrophil infiltration and the cognitive deficits associated with SAH. The re-introduction of biologically active MPO, and its substrate hydrogen peroxide, to the cerebrospinal fluid of MPO KO mice at the time of hemorrhage restores the spatial memory deficit observed after SAH. Furthermore, in culture, MPO affects the function of both primary neurons and astrocytes, though not microglia. Neurons exposed to MPO and its substrate show decreased calcium activity at baseline and after stimulation with potassium chloride. In addition, MPO and its substrate lead to significant astrocyte loss in culture, phenocopying a result observed in the brain after SAH. Conclusions: These results implicate MPO as a mediator of neuronal dysfunction in SAH through their effect on both neurons and astrocytes. Finally, these results show that, in SAH, the activity of innate immune cells in the meninges can modulate the activity and function of the underlying brain tissue.


Author(s):  
Dhurgham Khudhair ◽  
Julie Gaburro ◽  
Hoda Amani Hamedani ◽  
Anders Barlow ◽  
Hamid Garmestai ◽  
...  

Direct interaction with the neuronal cells is a prerequisite to deciphering useful information in understanding the underlying causes of diseases and functional abnormalities in the brain. Precisely fabricated nanoelectrodes provide the capability to interact with the brain in its natural habitat without compromising its functional integrity. Considerable research has been focused on the employment of vertical nanotubes as nanoelectrodes due to large-scale intracellular recording capability and longer-term intracellular access that arise from their unique geometry. Despite many types of nanotube structures reported in the literature, a limited subset of the nanotubes has been investigated for neural interfacing. This work reports on the fabrication and optimisation of vertically oriented titania nanotube arrays as a scalable electrode platform for neural interface application. To this end, the doping was performed by incorporating a selected group of biologically active metallic ions, including zinc, strontium, and copper, into TiO2 lattice and its effect was studied with respect to the structural, electrochemical and biological properties of the nanotube arrays. It was found that doping can change the length, diameter and wall thickness of the nanotubes. Among pure and doped samples, the copper-doped TiO2 nanotubes demonstrated the highest electrochemical and biological performance. Our results suggest that the doping can be used as a promising method to optimise the properties of nanotube arrays for the development of high-performance neural electrodes.


2014 ◽  
Vol 60 (5) ◽  
pp. 548-552
Author(s):  
N.A. Pravosudova ◽  
I.O. Bykova

The influence of a single injection of haloperidol on basic carboxypeptidases (biologically active peptide processing enzymes) activity in rat tissues was studied. Acute exposure to haloperidol increased the activity of carboxypeptidases H (CP H) in hypothalamic-pituitary-adrenal system and cerebellum and reduced such activity in testes. Multidirectional changes of PMSF-inhibited carboxypeptidases activity (PMSF-CP) were observed after a single haloperidol injection in all studied tissues except testes. It is suggested that changes of CP H and PMSF-CP activity might affect levels of regulatory peptides in the brain and blood and thus may be involved in general and side effects of haloperidol on the organism.


2019 ◽  
Vol 65 (3) ◽  
pp. 180-201 ◽  
Author(s):  
K.V. Shevchenko ◽  
I.Yu. Nagaev ◽  
L.A. Andreeva ◽  
V.P. Shevchenko ◽  
N.F. Myasoedov

New data on peptide drugs have been summarized; their high stability is due to both the introduction of Pro-Gly-Pro in various amino acid sequences and the modification of the glyproline fragment itself. Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 were used as proline-containing peptides. Tritiated peptides were obtained: Pro-Gly-Pro-Leu with specific radioactivity of 135 Ci/mmol, ACTH(6-9)Pro-Gly-Pro – 26 Ci/mmol, 5-oxo-Pro-Arg-Pro – 60 Ci/mmol and 5-oxo-Pro-His-Pro-NH2 – 75 Ci/mmol. The concentration of Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 in the blood was found to be about 200 times more than in the brain for intranasal administration, and in average 600 times more for intravenous administration. The stability of proline-containing peptides in vitro experiments was determined using different commercially available peptidases (leucine aminopeptidases, dipeptidases, carboxypeptidases B and Y), and using nasal mucus, microsomal fraction of the rat brain (IMPC) and rat blood plasma. During peptidase hydrolysis of Pro-Gly-Pro-Leu, the main metabolites were Gly-Pro-Leu, Pro-Gly-Pro, Gly-Pro and Pro-Gly. For ACTH(6-9)Pro-Gly-Pro, the main metabolites were Phe-Arg-Trp-Pro-Gly-Pro and Trp-Pro-Gly-Pro. In peptidase hydrolysis of 5-oxo-Pro-His-Pro-NH2, the major metabolite was 5-oxo-Pro-His-Pro. It was shown that with different methods of peptides administration the composition of the metabolites formed is different. Based on the data obtained, resistance to enzymatic cleavage of peptides and their metabolic pathways were evaluated. Thus, these new data have shown that the above approaches can be used to prolong the action of glyprolines in living objects. In this case, the degradation of proline-containing peptides occurs mainly not due to the action of proteases, but due to other ways of degradation. In general, the data presented in the review indicate the promise of intranasal way of introducing biologically active peptides into the brain of living organisms.


1984 ◽  
Vol 102 (1) ◽  
pp. 63-NP ◽  
Author(s):  
F. Moos ◽  
M. J. Freund-Mercier ◽  
Y. Guerné ◽  
J. M. Guerné ◽  
M. E. Stoeckel ◽  
...  

ABSTRACT The release of endogenous oxytocin and vasopressin by rat paraventricular and supraoptic nuclei in vitro during a 10-min period, 30 min after beginning the incubation, was measured radioimmunologically. Mean basal hormone release per 10 min and per pair of nuclei was: 128·4 ± 12·4 (s.e.m.) pg vasopressin (n = 15) and 39·0 ± 3·0 pg oxytocin (n = 66) for supraoptic nuclei from male rats; 273·9 ± 42·6 pg vasopressin (n = 11) and 34·2 ± 3·5 pg oxytocin (n = 15) for supraoptic nuclei from lactating rats; 70·0 ± 8·6 pg vasopressin (n = 52) and 21·8 ± 1·3 pg oxytocin (n = 68) for paraventricular nuclei from male rats; 59·1 ± 8·6 pg vasopressin (n = 10) and 27·0 ± 4·6 pg oxytocin (n = 16) for paraventricular nuclei from lactating rats. In male and lactating rats, both nuclei contained and released more vasopressin than oxytocin. For oxytocin alone, the paraventricular nucleus of male rats contained and released significantly less hormone than the supraoptic nucleus. This difference was not apparent in lactating rats. For vasopressin alone, the paraventricular nucleus contained and released significantly less hormone than the supraoptic nucleus in both male and lactating rats. When the hormone released was calculated as a percentage of the total tissue content the release was about 0·9% for oxytocin from both nuclei in male and lactating rats and also for vasopressin in lactating rats, but was only about 0·5% for vasopressin from both nuclei in male rats. The influence of oxytocin and analogues of oxytocin (including one antagonist) upon the release of oxytocin and vasopressin was studied. Adding oxytocin to the incubation medium (0·4–4 nmol/l solution) induced a dose-dependent rise in oxytocin release from both nuclei of male or lactating rats. A 4 nmol/l solution of isotocin had a similar effect to a 0·4 nmol/l solution of oxytocin, but arginine-vasopressin never affected basal release of oxytocin. In no case was vasopressin release modified. An oxytocin antagonist (1 μmol/l solution) significantly reduced basal oxytocin release and blocked the stimulatory effect normally induced by exogenous oxytocin, as did gallopamil hydrochloride (D600, 10 μmol/l solution), a Ca2+ channel blocker, or incubation in a Ca2+-free medium. These findings are discussed in relation to the literature on the central effects of neurohypophysial peptides. It may be concluded that the regulatory role of endogenous oxytocin in the hypothalamus on the milk-ejection reflex could result from its local release in the extracellular spaces of magnocellular nuclei. J. Endocr. (1984) 102, 63–72


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