scholarly journals The Neural Network of Neuropeptide S (NPS): Implications in Food Intake and Gastrointestinal Functions

2021 ◽  
Vol 14 (4) ◽  
pp. 293
Author(s):  
Luca Botticelli ◽  
Emanuela Micioni Di Bonaventura ◽  
Massimo Ubaldi ◽  
Roberto Ciccocioppo ◽  
Carlo Cifani ◽  
...  
Keyword(s):  
Food Intake ◽  
Drugs Of Abuse ◽  
Potential Interaction ◽  
Neuropeptide S ◽  
Behavioral Arousal ◽  
Brain Functions ◽  
The Neural Network ◽  
Anorexigenic Effect ◽  
G Protein Coupled

The Neuropeptide S (NPS), a 20 amino acids peptide, is recognized as the endogenous ligand of a previously orphan G protein-coupled receptor, now termed NPS receptor (NPSR). The limited distribution of the NPS-expressing neurons in few regions of the brainstem is in contrast with the extensive expression of NPSR in the rodent central nervous system, suggesting the involvement of this receptor in several brain functions. In particular, NPS promotes locomotor activity, behavioral arousal, wakefulness, and unexpectedly, at the same time, it exerts anxiolytic-like properties. Intriguingly, the NPS system is implicated in the rewarding properties of drugs of abuse and in the regulation of food intake. Here, we focus on the anorexigenic effect of NPS, centrally injected in different brain areas, in both sated and fasted animals, fed with standard or palatable food, and, in addition, on its influence in the gastrointestinal tract. Further investigations, regarding the role of the NPS/NPSR system and its potential interaction with other neurotransmitters could be useful to understand the mechanisms underlying its action and to develop novel pharmacological tools for the treatment of aberrant feeding patterns and obesity.

scholarly journals Neuromedin S Is a Novel Anorexigenic Hormone

Endocrinology ◽  
2005 ◽  
Vol 146 (10) ◽  
pp. 4217-4223 ◽  
Author(s):  
Takanori Ida ◽  
Kenji Mori ◽  
Mikiya Miyazato ◽  
Yutaka Egi ◽  
Shinsuke Abe ◽  
...  
Keyword(s):  
Food Intake ◽  
Physiological Role ◽  
The Novel ◽  
Feeding Regulation ◽  
Before And After ◽  
Multiple Unit ◽  
Anorexigenic Effect ◽  
Agouti Related Protein ◽  
G Protein Coupled

A novel 36-amino acid neuropeptide, neuromedin S (NMS), has recently been identified in rat brain and has been shown to be an endogenous ligand for two orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1. These receptors have been identified as neuromedin U (NMU) receptor type 1 and type 2, respectively. In this study, the physiological role of the novel peptide, NMS, on feeding regulation was investigated. Intracerebroventricular (icv) injection of NMS decreased 12-h food intake during the dark period in rats. This anorexigenic effect was more potent and persistent than that observed with the same dose of NMU. Neuropeptide Y, ghrelin, and agouti-related protein-induced food intake was counteracted by coadministration of NMS. Icv administration of NMS increased proopiomelanocortin mRNA expression in the arcuate nucleus (Arc) and CRH mRNA in the paraventricular nucleus (PVN). Pretreatment with SHU9119 (antagonist for α-MSH) and α-helical corticotropin-releasing factor-(9–41) (antagonist for CRH) attenuated NMS-induced suppression of 24-h food intake. After icv injection of NMS, Fos-immunoreactive cells were detected in both the PVN and Arc. When neuronal multiple unit activity was recorded in the PVN before and after icv injection of NMS, a significant increase in firing rate was observed 5 min after administration, and this increase continued for 100 min. These results suggest that the novel peptide, NMS, may be a potent anorexigenic hormone in the hypothalamus, and that expression of proopiomelanocortin mRNA in the Arc and CRH mRNA in the PVN may be involved in NMS action on feeding.

scholarly journals Structural and Functional Features of the P2X4 Receptor: An Immunological Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Jean M. Kanellopoulos ◽  
Cássio Luiz Coutinho Almeida-da-Silva ◽  
Sirje Rüütel Boudinot ◽  
David M. Ojcius
Keyword(s):  
Plasma Membrane ◽  
P2y Receptors ◽  
Potential Interaction ◽  
The Body ◽  
Extracellular Nucleotides ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Functional Features ◽  
G Protein Coupled

Extracellular nucleotides are important mediators of activation, triggering various responses through plasma membrane P2 and P1 receptors. P2 receptors are further subdivided into ionotropic P2X receptors and G protein-coupled P2Y receptors. P2X4 is an ATP-gated cation channel broadly expressed in most tissues of the body. Within the P2X family, P2X4 has a unique subcellular distribution, being preferentially localized in lysosomes. In these organelles, high ATP concentrations do not trigger P2X4 because of the low pH. However, when the pH increases to 7.4, P2X4 can be stimulated by intra-lysosomal ATP, which is in its active, tetra-anionic form. Elucidation of P2X4, P2X3 and P2X7 structures has shed some light on the functional differences between these purinergic receptors. The potential interaction between P2X4 and P2X7 has been extensively studied. Despite intensive effort, it has not been possible yet to determine whether P2X4 and P2X7 interact as heterotrimers or homotrimers at the plasma membrane. However, several publications have shown that functional interactions between P2X4 and P2X7 do occur. Importantly, these studies indicate that P2X4 potentiates P2X7-dependent activation of inflammasomes, leading to increased release of IL-1β and IL-18. The role of P2X4 in various diseases could be beneficial or deleterious even though the pathophysiological mechanisms involved are still poorly defined. However, in diseases whose physiopathology involves activation of the NLRP3 inflammasome, P2X4 was found to exacerbate severity of disease. The recent production of monoclonal antibodies specific for the human and mouse P2X4, some of which are endowed with agonist or antagonist properties, raises the possibility that they could be used therapeutically. Analysis of single nucleotide polymorphisms of the human P2RX4 gene has uncovered the association of P2RX4 gene variants with susceptibility to several human diseases.

scholarly journals Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Ken-ichiro Nakajima ◽  
Zhenzhong Cui ◽  
Chia Li ◽  
Jaroslawna Meister ◽  
Yinghong Cui ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Potential Role ◽  
G Protein Coupled Receptors ◽  
Signalling Cascades ◽  
Treatment Of Obesity ◽  
G Protein Coupled ◽  
Stimulation Of ◽  
Sustained Increase

Abstract Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.

scholarly journals The role of nociceptin in opioid regulation of brain functions

2021 ◽  
Vol 67 (1) ◽  
pp. 5-16
Author(s):  
I.Yu. Shamakina ◽  
F.Sh. Shagiakhmetov ◽  
P.K. Anokhin ◽  
V.S. Kohan ◽  
T.V. Davidova
Keyword(s):  
Drugs Of Abuse ◽  
Current Knowledge ◽  
Opioid Peptide ◽  
Brain Regions ◽  
Depression And Anxiety ◽  
Brain Functions ◽  
Affinity Ligand ◽  
High Level ◽  
High Affinity Ligand

This review discusses our current knowledge on the nociceptin/orphanin (N/OFQ) system regarding its role in regulation of brain functions. Nociceptin receptor (NOPr) was identified in 1994 [Bunzow et al., 1994; Mollereau et al., 1994]. In 1995 a 17 amino acid endogenous peptide was found to be the high-affinity ligand for the NOPr [Reinscheid et al., 1995]. N/OFQ has a broad spectrum of activity and can act as on opioid-like as well as an anti-opioid peptide. Considering high level of N/OFQ and NOPr mRNA expression in the limbic brain regions, the N/OFQ/NOP system is suggested to be involved in regulation of emotions, resward, pain sensitivity, stress responsibility, sexual behavior, aggression, drug abuse and addiction. However it is still not well understood whether an increased vulnerability to drugs of abuse may be associated with dysregulation of N/OFQ/NOP system. Current review further highlights a need for further research on N/OFQ/NOP system as it could have clinical utility for substance abuse, depression, and anxiety pharmacotherapy.

Effect of amphetamine on food intake in rats with brain-stem lesions

1961 ◽  
Vol 201 (5) ◽  
pp. 965-967 ◽  
Author(s):  
Harry J. Carlisle ◽  
Robert W. Reynolds
Keyword(s):  
Food Intake ◽  
Weight Control ◽  
Area Postrema ◽  
Drug Action ◽  
Facilitatory Effect ◽  
Target Area ◽  
Stem Lesions ◽  
Anorexigenic Effect ◽  
Slight Amount

An examination was made of the role of the area postrema in the regulation of food intake and in mediating the anorexigenic effect of amphetamine. Rats with area postrema lesions lost 13–20% of preoperative weight, and tended to regain only a slight amount of this lost weight. Control lesions in the hippocampus and dorsolateral thalamus produced no significant effect on food intake. It was concluded that the area postrema has a facilitatory effect on food intake. The anorexigenic effect of amphetamine was exaggerated in the area postrema group with 50% or greater damage to the target area only. This area is not, therefore, a primary receptor for amphetamine, but is somehow implicated, since its destruction results in greater drug action.

scholarly journals Brain-Derived Neurotrophic Factor/Tropomyosin-Related Kinase Receptor Type B Signaling Is a Downstream Effector of the Brainstem Melanocortin System in Food Intake Control

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2646-2653 ◽  
Author(s):  
Bruno Bariohay ◽  
Julien Roux ◽  
Catherine Tardivel ◽  
Jérôme Trouslard ◽  
Andre Jean ◽  
...  
Keyword(s):  
Food Intake ◽  
Protein Content ◽  
Signaling Pathway ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Type B ◽  
Downstream Effector ◽  
Anorexigenic Effect ◽  
Intake Control

It has been shown that the neurotropin brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin-related kinase receptor type B (TrkB), contribute to the central control of food intake. BDNF has previously been implicated as a probable downstream effector of melanocortinergic signaling within the ventromedial hypothalamus, and we have shown its implication as an anorexigenic factor within the brainstem autonomic integrator of food intake control, namely the dorsal vagal complex (DVC). In the brainstem, the melanocortinergic signaling pathway is known to integrate phasic responses to satiety signals, such as cholecystokinin. In this study, we explored the interactions between melanocortin and BDNF/TrkB signaling within the DVC. First, we tested the effect of a local pharmacological activation or inhibition of melanocortin receptors type 3/4 (MC3/4R) on BDNF protein content in the DVC of adult rats. We showed that fourth intracerebroventricular delivery of MC3/4R agonist and antagonist increased and decreased the BDNF protein content within the DVC, respectively. Second, we showed that the orexigenic effect of a selective MC4R antagonist delivered fourth-icv can be blocked by a coadministration of BDNF. We also tested the causal role of BDNF/TrkB signaling in the anorexigenic effect of melanocortinergic signaling by using a recently developed analog-sensitive kinase allele murine model (TrkBF616A mice) and showed that the pharmacological blockade of TrkB abolished the anorexigenic effect of a selective MC4R agonist and of cholecystokinin. Our results provide strong evidence for a role of BDNF as a downstream effector of melanocortinergic signaling pathway within the DVC.

scholarly journals The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) influences age at onset of obsessive–compulsive disorder

2013 ◽  
Vol 16 (9) ◽  
pp. 1951-1958 ◽  
Author(s):  
Leonhard Lennertz ◽  
Petra E. Franke ◽  
Hans Jörgen Grabe ◽  
Friederike Rampacher ◽  
Svenja Schulze-Rauschenbach ◽  
...  
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Early Onset ◽  
Late Onset ◽  
Receptor Gene ◽  
Age At Onset ◽  
Neuropeptide S ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Brain Functions

Abstract Neuropeptide S (NPS) is a novel central acting neuropeptide that modulates several brain functions. NPS has shown strong anxiolytic-like effects and interactions with other central transmitter systems, including serotonin and glutamate. A coding variation (Asn107Ile) of the NPS receptor gene (NPSR1) was associated with panic disorder and schizophrenia. Based on these encouraging findings, the present study aimed at exploring a potential role of NPSR1 in obsessive–compulsive disorder (OCD). A sample of 232 OCD patients was successfully genotyped for the NPSR1 Asn107Ile variant (rs324981). Age at onset was taken into account to address the heterogeneity of the OCD phenotype. The NPSR1 genotype significantly affected age at onset of the OCD patients, with a mean age at onset approximately 4 yr earlier in homozygous carriers of the low-functioning Asn107 variant compared to patients with at least one Ile107 variant (p = 0.032). Case–control analyses with 308 healthy control subjects reveal a highly significant association of the Asn107 variant with early onset OCD (odds ratio = 2.36, p = 0.0004) while late onset OCD or the OCD group as a whole were unrelated to the NPSR1 genotype. Based on our association finding relating NPSR1 genotype to early onset OCD, we suggest a differential role of the NPS system in OCD. In particular, the early onset OCD subtype seems to be characterized by a genetically driven low NPS tone, which might affect other OCD-related transmitter systems, including the serotonin and glutamate systems. In agreement with preclinical research, we suggest that NPS may be a promising pharmacological candidate with anti-obsessional properties.

Anorexigenic substances and voluntary food intake in the pig

1978 ◽  
Vol 26 (1) ◽  
pp. 19-29 ◽  
Author(s):  
D. Wyllie ◽  
J. B. Owen
Keyword(s):  
Food Intake ◽  
Distilled Water ◽  
Rat Urine ◽  
Urine Extract ◽  
Ad Libitum ◽  
Anorexigenic Effect ◽  
Dose Dependent ◽  
Voluntary Food Intake

ABSTRACTThe urine of pigs contains a substance with an anorexigenic effect when injected into pigs or rats. When injected into rats or pigs on ad libitum feeding a urine extract caused a reduction in food intake only when the extract had been obtained from the urine of satiated pigs, and not from hungry pigs. The pig urinary anorexigen there-fore appears to be similar in nature to the anorexigen extracted from rat urine. Like rat urinary anorexigen, its anorexigenic effect is largely dose dependent and it is soluble in distilled water. Rats injected with plasma from satiated pigs showed an anorexigenic reaction but injection of plasma from hungry pigs had no effect on food intake. The possible role of these anorexigenic substances in the control of voluntary food intake in the pig is discussed.

scholarly journals Normal Food Intake and Body Weight in Mice Lacking the G Protein-Coupled Receptor GPR39

Endocrinology ◽  
2007 ◽  
Vol 148 (2) ◽  
pp. 501-506 ◽  
Author(s):  
Frédéric Tremblay ◽  
Mylène Perreault ◽  
Lori D. Klaman ◽  
James F. Tobin ◽  
Erica Smith ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
G Protein ◽  
Ectopic Expression ◽  
Phenotypic Characterization ◽  
Wild Type ◽  
G Protein Coupled Receptor ◽  
Multiple Sources ◽  
G Protein Coupled

It has been recently proposed that obestatin, a peptide encoded by the ghrelin gene, reduces food intake by activating the orphan G protein-coupled receptor GPR39. To gain further insights into the role of GPR39 in body weight homeostasis, we characterized the phenotype of mice with targeted disruption of the GPR39 gene. Body weight, adiposity, and food intake were found to be similar between GPR39+/+ and GPR39−/− mice. Furthermore, fasting glucose and insulin levels were similar between both genotypes. Injection of obestatin peptide (1 μmol/kg, ip) obtained from multiple sources did not consistently inhibit food intake in wild-type mice after an overnight fast, and no difference in food intake was observed between wild-type and GPR39 knockout mice after injection of the peptide. Finally, ectopic expression of GPR39 in HEK293T cells revealed a constitutive activation of the receptor that was unaffected by stimulation with obestatin. Our phenotypic characterization suggests that GPR39 is not a major modulator of food intake in mice, although a more subtle role cannot be excluded. The role of GPR39 in normal physiology requires further study and should be conducted independently of the function of obestatin.

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