Neuromedins NMU and NMS: An Updated Overview of Their Functions

G Protein Coupled ◽

Insight Into

More than 35 years have passed since the identification of neuromedin U (NMU). Dozens of publications have been devoted to its physiological role in the organism, which have provided insight into its occurrence in the body, its synthesis and mechanism of action at the cellular level. Two G protein-coupled receptors (GPCRs) have been identified, with NMUR1 distributed mainly peripherally and NMUR2 predominantly centrally. Recognition of the role of NMU in the control of energy homeostasis of the body has greatly increased interest in this neuromedin. In 2005 a second, structurally related peptide, neuromedin S (NMS) was identified. The expression of NMS is more restricted, it is predominantly found in the central nervous system. In recent years, further peptides related to NMU and NMS have been identified. These are neuromedin U precursor related peptide (NURP) and neuromedin S precursor related peptide (NSRP), which also exert biological effects without acting via NMUR1, or NMUR2. This observation suggests the presence of another, as yet unrecognized receptor. Another unresolved issue within the NMU/NMS system is the differences in the effects of various NMU isoforms on diverse cell lines. It seems that development of highly specific NMUR1 and NMUR2 receptor antagonists would allow for a more detailed understanding of the mechanisms of action of NMU/NMS and related peptides in the body. They could form the basis for attempts to use such compounds in the treatment of disorders, for example, metabolic disorders, circadian rhythm, stress, etc.

The Role of Neuropeptide B and Its Receptors in Controlling Appetite, Metabolism and Energy Homeostasis

International Journal of Molecular Sciences ◽

10.3390/ijms22126632 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6632

Author(s):

Tatiana Wojciechowicz ◽

Maria Billert ◽

Mariami Jasaszwili ◽

Mathias Z. Strowski ◽

Krzysztof W. Nowak ◽

...

Keyword(s):

Pancreatic Beta Cells ◽

Energy Homeostasis ◽

Biological Effects ◽

Peptide Hormone ◽

Peripheral Tissues ◽

Adrenal Hormones ◽

Pain Anxiety ◽

Neuropeptide B (NPB) is a peptide hormone that was initially described in 2002. In humans, the biological effects of NPB depend on the activation of two G protein-coupled receptors, NPBWR1 (GPR7) and NPBWR2 (GPR8), and, in rodents, NPBWR1. NPB and its receptors are expressed in the central nervous system (CNS) and in peripheral tissues. NPB is also present in the circulation. In the CNS, NPB modulates appetite, reproduction, pain, anxiety, and emotions. In the peripheral tissues, NPB controls secretion of adrenal hormones, pancreatic beta cells, and various functions of adipose tissue. Experimental downregulation of either NPB or NPBWR1 leads to adiposity. Here, we review the literature with regard to NPB-dependent control of metabolism and energy homeostasis.

Role of Cannabinoid Receptors in Psychological Disorder

Borneo Journal of Pharmacy ◽

10.33084/bjop.v3i4.1569 ◽

2020 ◽

Vol 3 (4) ◽

pp. 199-208

Author(s):

Ambika Nand Jha ◽

Dhaval M Patel

Keyword(s):

Cannabinoid Receptors ◽

Biological Effects ◽

Endocannabinoid System ◽

Brain Regions ◽

The Body ◽

Psychological Disorder ◽

Physiological Processes ◽

Neurochemical Changes ◽

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system. Cannabinoid CB1 and CB2 receptors are G protein-coupled receptors present from the early stages of gestation, which is involved in various physiological processes, including appetite, pain-sensation, mood, and memory. Due to the lipophilic nature of cannabinoids, it was initially thought that these compounds exert several biological effects by disrupting the cell membrane nonspecifically. Recent biochemical and behavioral findings have demonstrated that blockade of CB1 receptors engenders antidepressant-like neurochemical changes (increases in extracellular levels of monoamines in cortical but not subcortical brain regions) and behavioral effects consistent with antidepressant/antistress activity. We aim to define various roles of cannabinoid receptors in modulating signaling pathways and association with several pathophysiological conditions.

The role of orexin in controlling the activity of the adipo-pancreatic axis

Journal of Endocrinology ◽

10.1530/joe-18-0122 ◽

2018 ◽

Vol 238 (2) ◽

pp. R95-R108 ◽

Cited By ~ 4

Author(s):

M Skrzypski ◽

M Billert ◽

K W Nowak ◽

M Z Strowski

Keyword(s):

Energy Homeostasis ◽

Current Knowledge ◽

Biological Effects ◽

Peripheral Tissues ◽

Cell Functions ◽

White Adipocytes ◽

Obesity And Diabetes ◽

Regulate Body Weight ◽

Orexin A and B are two neuropeptides, which regulate a variety of physiological functions by interacting with central nervous system and peripheral tissues. Biological effects of orexins are mediated through two G-protein-coupled receptors (OXR1 and OXR2). In addition to their strong influence on the sleep–wake cycle, there is growing evidence that orexins regulate body weight, glucose homeostasis and insulin sensitivity. Furthermore, orexins promote energy expenditure and protect against obesity by interacting with brown adipocytes. Fat tissue and the endocrine pancreas play pivotal roles in maintaining energy homeostasis. Since both organs are crucially important in the context of pathophysiology of obesity and diabetes, we summarize the current knowledge regarding the role of orexins and their receptors in controlling adipocytes as well as the endocrine pancreatic functions. Particularly, we discuss studies evaluating the effects of orexins in controlling brown and white adipocytes as well as pancreatic alpha and beta cell functions.

Neuromediators and neuropeptides: the biomarkers for metabolic disturbances in obesity

Problems of Endocrinology ◽

10.14341/probl9466 ◽

2018 ◽

Vol 64 (4) ◽

pp. 258-269 ◽

Cited By ~ 1

Author(s):

Ivan V. Gmoshinski ◽

Sergey A. Apryatin ◽

Vladimir A. Shipelin ◽

Dmitriy B. Nikitjuk

Keyword(s):

Metabolic Regulation ◽

Energy Homeostasis ◽

Cannabinoid Receptors ◽

Diet Therapy ◽

Experimental Models ◽

The Body ◽

Metabolic Disturbances ◽

Clinical Observations ◽

The role of biogenic amines (serotonin, dopamine) and neuropeptides in regulation of energy homeostasis of the organism and their role as markers of metabolic disorders in obesity (Ob) in animal experimental models and in clinical observations is reviewed. The energy homeostasis of the body is controlled via competition of alternative regulatory mechanisms that are mainly localized in the hypothalamus (HT). At the level of aminergic regulation, these are the serotonin and dopamine systems; at the level of the peptidergic system, these are NPY/AgRP and POMC/CART-related peptides. Opioid and cannabinoid receptors and their endogenous ligands closely linked to peptidergic and aminergic regulatory subsystems of the central nervous system ensure the connection between the «metabolic» regulation loop responding to a deficit or excess of energy substrates the «hedonistic» one associated with the body’s perception of pleasure from food consumption. The response of peptidergic and aminergic HT neurons to food and hormonal signals originating from the outside is based on the interaction between the corresponding ligands and G-protein-coupled receptors specific to them. Disruption or breakdown of the central mechanisms is considered to be one of the main pathogenetic factors of obesity and, simultaneously, the reason why reducing diet therapy proves inefficient or unstable. Partial permeability of the blood—brain barrier for neuropeptides makes them an attractive biomarker in the diagnosis of metabolic abnormalities in obese patients.

The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

Frontiers in Pharmacology ◽

10.3389/fphar.2021.640441 ◽

2021 ◽

Vol 12 ◽

Author(s):

Roberta Lattanzi ◽

Cinzia Severini ◽

Daniela Maftei ◽

Luciano Saso ◽

Aldo Badiani

Keyword(s):

Pain Perception ◽

G Protein Coupled Receptors ◽

Cellular Processes ◽

Prokineticin 2 ◽

Physiological Processes ◽

Pathological Conditions ◽

Double Function ◽

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

Exploring Ligand Binding to Calcitonin Gene-Related Peptide Receptors

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.720561 ◽

2021 ◽

Vol 8 ◽

Author(s):

Giuseppe Deganutti ◽

Silvia Atanasio ◽

Roxana-Maria Rujan ◽

Patrick M. Sexton ◽

Denise Wootten ◽

...

Keyword(s):

Molecular Dynamics ◽

Ligand Binding ◽

Calcitonin Gene Related Peptide ◽

Related Peptide ◽

Calcitonin Gene ◽

Approved Drugs ◽

G Protein Coupled ◽

Dynamic Docking ◽

Receptor Family

Class B1 G protein-coupled receptors (GPCRs) are important targets for many diseases, including cancer, diabetes, and heart disease. All the approved drugs for this receptor family are peptides that mimic the endogenous activating hormones. An understanding of how agonists bind and activate class B1 GPCRs is fundamental for the development of therapeutic small molecules. We combined supervised molecular dynamics (SuMD) and classic molecular dynamics (cMD) simulations to study the binding of the calcitonin gene-related peptide (CGRP) to the CGRP receptor (CGRPR). We also evaluated the association and dissociation of the antagonist telcagepant from the extracellular domain (ECD) of CGRPR and the water network perturbation upon binding. This study, which represents the first example of dynamic docking of a class B1 GPCR peptide, delivers insights on several aspects of ligand binding to CGRPR, expanding understanding of the role of the ECD and the receptor-activity modifying protein 1 (RAMP1) on agonist selectivity.

Folic acid – role in the body, recommendations and clinical significance

Pielegniarstwo XXI wieku / Nursing in the 21st Century ◽

10.2478/pielxxiw-2019-0007 ◽

2019 ◽

Vol 18 (1) ◽

pp. 50-59 ◽

Cited By ~ 1

Author(s):

Aneta Myszczyszyn ◽

Rafał Krajewski ◽

Monika Ostapów ◽

Lidia Hirnle

Keyword(s):

Folic Acid ◽

Biological Effects ◽

Folic Acid Supplementation ◽

The Body ◽

Leafy Vegetables ◽

Congenital Defects ◽

Natural Form ◽

Vitamin B9 ◽

Increased Risk

AbstractIntroduction. Folic acid is a compound classified as B group vitamins. In the body it is subject to processes that transfer its inactive form into a form responsible for biological effects of folic acid, i.e. 5-methyltetrahydrofolate (5-MTHF). It is, in particular, responsible for processes of the correct biosynthesis of purine and pyridine bases present in the formation of DNA and RNA molecules. Humans do not synthesize the endogenous form of folic acid; therefore, it is vital to supplement this vitamin in its natural form or multivitamin preparations. The most folic acid is found in the green leafy vegetables (spinach, peas, asparagus) and in offal (liver). An adequate supply of folic acid is especially indicated in pregnant women with a reduced amount of folic acid due to its use by an intensively developing foetus. The recommended dose of folic acid during this period is 0.4 mg/24h and this dose varies depending on the patient’s and her family’s medical history. The updated state of knowledge on the role of vitamin B9 in the body has been presented. The importance of its supplementation in specific clinical cases was analyzed.Summary. Many studies indicate an important role of the folic acid in the prevention of congenital defects of the nervous, cardiovascular and urogenital systems. Its deficiency increases the risk of complications in pregnancy, such as recurrent miscarriages, pre-eclampsia or postpartum haemorrhage. For this reason, a prophylactic folic acid supplementation is recommended, in women with increased risk of its deficiency, in particular.

Insight into the physiological role of a compartmentalised ferritin like protein in Rhodospirillum rubrum

New Biotechnology ◽

10.1016/j.nbt.2014.05.1711 ◽

2014 ◽

Vol 31 ◽

pp. S43-S44

Author(s):

Jon Marles-Wright ◽

Didi He ◽

Atanas Georgiev ◽

David Clarke

Keyword(s):

Rhodospirillum Rubrum ◽

Physiological Role ◽

Insight Into

Store-Operated Calcium Channels in Physiological and Pathological States of the Nervous System

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2020.600758 ◽

2020 ◽

Vol 14 ◽

Author(s):

Isis Zhang ◽

Huijuan Hu

Keyword(s):

Nervous System ◽

Calcium Channels ◽

Neurological Disorders ◽

Neurological Diseases ◽

Physiological Role ◽

The Body ◽

Store Operated Calcium Entry ◽

Important Pathway ◽

Molecular Components

Store-operated calcium channels (SOCs) are widely expressed in excitatory and non-excitatory cells where they mediate significant store-operated calcium entry (SOCE), an important pathway for calcium signaling throughout the body. While the activity of SOCs has been well studied in non-excitable cells, attention has turned to their role in neurons and glia in recent years. In particular, the role of SOCs in the nervous system has been extensively investigated, with links to their dysregulation found in a wide variety of neurological diseases from Alzheimer’s disease (AD) to pain. In this review, we provide an overview of their molecular components, expression, and physiological role in the nervous system and describe how the dysregulation of those roles could potentially lead to various neurological disorders. Although further studies are still needed to understand how SOCs are activated under physiological conditions and how they are linked to pathological states, growing evidence indicates that SOCs are important players in neurological disorders and could be potential new targets for therapies. While the role of SOCE in the nervous system continues to be multifaceted and controversial, the study of SOCs provides a potentially fruitful avenue into better understanding the nervous system and its pathologies.

Biological effects of xenoestrogens and the functional mechanisms via genomic and nongenomic pathways

Environmental Reviews ◽

10.1139/er-2016-0075 ◽

2017 ◽

Vol 25 (3) ◽

pp. 306-322 ◽

Cited By ~ 11

Author(s):

Zhi-Xiang Xu ◽

Jun Liu ◽

Li-Peng Gu ◽

Bin Huang ◽

Xue-Jun Pan

Keyword(s):

Estrogen Receptor ◽

Estrogen Receptor Alpha ◽

Biological Effects ◽

Receptor Alpha ◽

Estrogenic Effects ◽

Immunological Effects ◽

Functional Mechanisms ◽

Nongenomic Effects ◽

G Protein Coupled ◽

Insight Into

Xenoestrogens (XEs) are a class of substances that exert estrogenic effects by mimicking or blocking endogenous hormones. The sources, environmental behavior, and fate of typical XEs are described. XEs’ adverse developmental, metabolic, and immunological effects are then presented with respect to reproductive functions. The mechanisms underlying XEs’ genomic and nongenomic effects are reviewed. XEs can alter gene transcription by interfering with the functioning of conventional estrogen receptors, but they are also capable of activating multiple kinase signaling pathways that disrupt membrane-associated receptors, such as estrogen receptor alpha-36 (ERα36), estrogen receptor alpha-46 (ERα46), and G protein-coupled receptor 30 (GPR30). This review aims to provide insight into XEs’ environmental effects and to explore the prevention and treatment of their estrogenic effects based on sufficient comprehension of the mechanisms involved.