Neuromedin U and Structural Analogs: An Overview of their Structure, Function and Selectivity

The neuromedin U peptide sequence is highly conserved between various species. Neuromedin U is involved in a variety of physiological processes. It exerts its effects via two neuromedin U receptors, NMUR1 and NMUR2. These receptors are characterized by a distinct, yet complementary, tissue distribution with NMUR1 mostly found in the periphery, while NMUR2 is most abundant in the central nervous system. The capability of the neuropeptide to reduce food intake in rodents triggered the design and synthesis of a broad range of modified peptide ligands. The purpose of these ligands is to develop novel therapeutics which could be beneficial in the treatment of obesity and diabetes. Most compounds are derived either from the full-length neuromedin U sequence or are based on the truncated orthologs of this neuropeptide. Only a few non-peptidic ligands were developed. This review provides an overview on various neuromedin U analogs and mimetics that have been reported to date.

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Drugs modulating the L-arginine:NO:cGMP pathway – current use in therapy

Current Issues in Pharmacy and Medical Sciences ◽

10.1515/cipms-2016-0004 ◽

2016 ◽

Vol 29 (1) ◽

pp. 14-20 ◽

Cited By ~ 3

Author(s):

Magdalena Polakowska ◽

Jolanta Orzelska-Gorka ◽

Sylwia Talarek

Keyword(s):

Nitric Oxide ◽

Central Nervous System ◽

Nervous System ◽

Cardiovascular Diseases ◽

Significant Role ◽

Current Understanding ◽

Physiological Processes ◽

Wide Range ◽

The Central Nervous System ◽

Pharmacological Profiles

AbstractNitric oxide (NO) is a relatively novel messenger that plays a significant role in a wide range of physiological processes. Currently, it is known that, both, lack and excess of NO can cause diseases, thus a lot of substances have been discovered and utilized which can change the concentration of this molecule within the organism. The aim of the present work is to provide an overview of currently used agents modulating the L-arginine:NO:cGMP pathway, as well as to summarize current understanding of their pharmacological profiles. Nowadays, most of these agents are employed particularly in the treatment of cardiovascular diseases. Further studies can hold promise for enhancing the therapeutic equipment for a variety of other impairments, such as osteoporosis, and also in treatments of the central nervous system.

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Molecular Mechanisms of Hypothalamic Insulin Resistance

International Journal of Molecular Sciences ◽

10.3390/ijms20061317 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1317 ◽

Cited By ~ 8

Author(s):

Hiraku Ono

Keyword(s):

Insulin Resistance ◽

Central Nervous System ◽

Nervous System ◽

Insulin Receptor ◽

Molecular Mechanisms ◽

Saturated Fatty Acids ◽

Saturated Fat ◽

Serine Phosphorylation ◽

Obesity And Diabetes ◽

The Central Nervous System

Insulin exists in the central nervous system, where it executes two important functions in the hypothalamus: the suppression of food intake and the improvement of glucose metabolism. Recent studies have shown that both are exerted robustly in rodents and humans. If intact, these functions exert beneficial effects on obesity and diabetes, respectively. Disruption of both occurs due to a condition known as hypothalamic insulin resistance, which is caused by obesity and the overconsumption of saturated fat. An enormous volume of literature addresses the molecular mechanisms of hypothalamic insulin resistance. IKKβ and JNK are major players in the inflammation pathway, which is activated by saturated fatty acids that induce hypothalamic insulin resistance. Two major tyrosine phosphatases, PTP-1B and TCPTP, are upregulated in chronic overeating. They dephosphorylate the insulin receptor and insulin receptor substrate proteins, resulting in hypothalamic insulin resistance. Prolonged hyperinsulinemia with excessive nutrition activates the mTOR/S6 kinase pathway, thereby enhancing IRS-1 serine phosphorylation to induce hypothalamic insulin resistance. Other mechanisms associated with this condition include hypothalamic gliosis and disturbed insulin transport into the central nervous system. Unveiling the precise molecular mechanisms involved in hypothalamic insulin resistance is important for developing new ways of treating obesity and type 2 diabetes.

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Identification and characterization of expression profiles of neuropeptides and their GPCRs in the swimming crab, Portunus trituberculatus

PeerJ ◽

10.7717/peerj.12179 ◽

2021 ◽

Vol 9 ◽

pp. e12179

Author(s):

Shisheng Tu ◽

Rui Xu ◽

Mengen Wang ◽

Xi Xie ◽

Chenchang Bao ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Expression Profile ◽

Expression Profiles ◽

Tissue Expression ◽

Portunus Trituberculatus ◽

Physiological Processes ◽

Tissue Expression Profile ◽

The Central Nervous System ◽

Reproductive Processes

Neuropeptides and their G protein-coupled receptors (GPCRs) regulate multiple physiological processes. Currently, little is known about the identity of native neuropeptides and their receptors in Portunus trituberculatus. This study employed RNA-sequencing and reverse transcription-polymerase chain reaction (RT-PCR) techniques to identify neuropeptides and their receptors that might be involved in regulation of reproductive processes of P. trituberculatus. In the central nervous system transcriptome data, 47 neuropeptide transcripts were identified. In further analyses, the tissue expression profile of 32 putative neuropeptide-encoding transcripts was estimated. Results showed that the 32 transcripts were expressed in the central nervous system and 23 of them were expressed in the ovary. A total of 47 GPCR-encoding transcripts belonging to two classes were identified, including 39 encoding GPCR-A family and eight encoding GPCR-B family. In addition, we assessed the tissue expression profile of 33 GPCRs (27 GPCR-As and six GPCR-Bs) transcripts. These GPCRs were found to be widely expressed in different tissues. Similar to the expression profiles of neuropeptides, 20 of these putative GPCR-encoding transcripts were also detected in the ovary. This is the first study to establish the identify of neuropeptides and their GPCRs in P. trituberculatus, and provide information for further investigations into the effect of neuropeptides on the physiology and behavior of decapod crustaceans.

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Molecular studies of CGRP and the CGRP family of peptides in the central nervous system

Cephalalgia ◽

10.1177/0333102418765787 ◽

2018 ◽

Vol 39 (3) ◽

pp. 403-419 ◽

Cited By ~ 20

Author(s):

Erica R Hendrikse ◽

Rebekah L Bower ◽

Debbie L Hay ◽

Christopher S Walker

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Calcitonin Gene Related Peptide ◽

Receptor Activity ◽

Peptide Sequence ◽

Calcitonin Receptor ◽

Related Peptide ◽

Calcitonin Gene ◽

The Central Nervous System ◽

Receptor Biology

Background Calcitonin gene-related peptide is an important target for migraine and other painful neurovascular conditions. Understanding the normal biological functions of calcitonin gene-related peptide is critical to understand the mechanisms of calcitonin gene-related peptide-blocking therapies as well as engineering improvements to these medications. Calcitonin gene-related peptide is closely related to other peptides in the calcitonin gene-related peptide family of peptides, including amylin. Relatedness in peptide sequence and in receptor biology makes it difficult to tease apart the contributions that each peptide and receptor makes to physiological processes and to disorders. Summary The focus of this review is the expression of calcitonin gene-related peptide, related peptides and their receptors in the central nervous system. Calcitonin gene-related peptide is expressed throughout the nervous system, whereas amylin and adrenomedullin have only limited expression at discrete sites in the brain. The components of two receptors that respond to calcitonin gene-related peptide, the calcitonin gene-related peptide receptor (calcitonin receptor-like receptor with receptor activity-modifying protein 1) and the AMY1 receptor (calcitonin receptor with receptor activity-modifying protein 1), are expressed throughout the nervous system. Understanding expression of the peptides and their receptors lays the foundation for more deeply understanding their physiology, pathophysiology and therapeutic use.

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Distribution of catecholamines in the sea scallop, Placopecten magellanicus

Canadian Journal of Zoology ◽

10.1139/z98-063 ◽

1998 ◽

Vol 76 (7) ◽

pp. 1254-1262 ◽

Cited By ~ 18

Author(s):

Stephanie A Smith ◽

Janette Nason ◽

Roger P Croll

Keyword(s):

Central Nervous System ◽

Nervous System ◽

High Performance ◽

Present Report ◽

Placopecten Magellanicus ◽

Peripheral Tissues ◽

Sea Scallop ◽

Physiological Processes ◽

Gill Filaments ◽

The Central Nervous System

Catecholamines have previously been implicated in several important physiological processes in molluscs, including reproduction, respiration, and feeding. Much of the previous research has relied upon high-performance liquid chromatography to identify and quantify the various catecholamines and pharmacological experiments to investigate their actions. In the present report, we expand upon these studies by using histochemical techniques to investigate the distribution of catecholamine-containing cells and fibres in the central nervous system and peripheral tissues of the sea scallop, Placopecten magellanicus. Strong catecholaminergic staining was present in the somata and neuropil of all major central ganglia. Catecholamines were also abundantly stained in peripheral neurones and (or) fibres in several other tissues, including the labial palps, lips, intestine, gill filaments, foot, mantle, tentacles, and gonadal integument. It is concluded that catecholamines are widespread in the tissues of the scallop and could have potential neurotransmission roles in both the central nervous system and peripheral tissues of this species.

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The hormonal coordination of behavior and physiology at adult ecdysis in Drosophila melanogaster

Journal of Experimental Biology ◽

10.1242/jeb.202.21.3037 ◽

1999 ◽

Vol 202 (21) ◽

pp. 3037-3048 ◽

Cited By ~ 16

Author(s):

J.D. Baker ◽

S.L. McNabb ◽

J.W. Truman

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Drosophila Melanogaster ◽

Cyclic Guanosine Monophosphate ◽

Guanosine Monophosphate ◽

Inhibitory Neurons ◽

Descending Inhibition ◽

Physiological Processes ◽

The Central Nervous System ◽

Ecdysis Triggering Hormone

In insects, ecdysis is thought to be controlled by the interaction between peptide hormones; in particular between ecdysis-triggering hormone (ETH) from the periphery and eclosion hormone (EH) and crustacean cardioactive peptide (CCAP) from the central nervous system. We examined the behavioral and physiological functions of the first two of these peptides in Drosophila melanogaster using wild-type flies and knockout flies that lacked EH neurons. We used ETH from Manduca sexta (MasETH) to induce premature ecdysis and compared the responses of the two types of flies. The final release of EH normally occurs approximately 40 min before ecdysis. It is correlated with cyclic guanosine monophosphate (cGMP) production in selected neurons and tracheae, by an elevation in the heart rate and by the filling of the new tracheae with air. Injection of developing flies with MasETH causes all these events to occur prematurely. In EH cell knockouts, none of these changes occurs in response to MasETH, and these flies show a permanent failure in tracheal filling. This failure can be overcome in the knockouts by injecting them with membrane-permeant analogs of cGMP, the second messenger for EH. The basis for the 40 min delay between EH release and the onset of ecdysis was examined by decapitating flies at various times relative to EH release. In flies that had already released EH, decapitation was always followed within 1 min by the start of ecdysis. Immediate ecdysis was never observed when the EH cell knockout flies were decapitated. We propose that EH activates both ventral central nervous system elements necessary for ecdysis (possibly the CCAP cells) and descending inhibitory neurons from the head. This descending inhibition establishes a delay in the onset of ecdysis that allows the completion of EH-activated physiological processes such as tracheal filling. A waning in the inhibition eventually allows ecdysis to begin 30–40 min later.

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Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Pharmaceutics ◽

10.3390/pharmaceutics12020192 ◽

2020 ◽

Vol 12 (2) ◽

pp. 192 ◽

Cited By ~ 2

Author(s):

Ana P. Spencer ◽

Marília Torrado ◽

Beatriz Custódio ◽

Sara C. Silva-Reis ◽

Sofia D. Santos ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Chemical Properties ◽

Neurologic Diseases ◽

Physiological Processes ◽

Specific Accumulation ◽

The Central Nervous System ◽

Clinical Interest ◽

Physical And Chemical ◽

Neuronal Delivery

Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.

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Interactions between the central nervous system and pancreatic islet secretions: a historical perspective

AJP Advances in Physiology Education ◽

10.1152/advan.00167.2012 ◽

2013 ◽

Vol 37 (1) ◽

pp. 53-60 ◽

Cited By ~ 27

Author(s):

Denovan P. Begg ◽

Stephen C. Woods

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Food Intake ◽

Gut Hormones ◽

The Body ◽

Endocrine Function ◽

Reduce Food Intake ◽

Diverse Range ◽

The Central Nervous System ◽

The Brain

The endocrine pancreas is richly innervated with sympathetic and parasympathetic projections from the brain. In the mid-20th century, it was established that α-adrenergic activation inhibits, whereas cholinergic stimulation promotes, insulin secretion; this demonstrated the importance of the sympathetic and parasympathetic systems in pancreatic endocrine function. It was later established that insulin injected peripherally could act within the brain, leading to the discovery of insulin and insulin receptors within the brain and the receptor-mediated transport of insulin into the central nervous system from endothelial cells. The insulin receptor within the central nervous system is widely distributed, reflecting insulin's diverse range of actions, including acting as an adiposity signal to reduce food intake and increase energy expenditure, regulation of systemic glucose responses, altering sympathetic activity, and involvement in cognitive function. As observed with central insulin administration, the pancreatic hormones glucagon, somatostatin, pancreatic polypeptide, and amylin can each also reduce food intake. Pancreatic and also gut hormones are released cephalically, in what is an important mechanism to prepare the body for a meal and prevent excessive postprandial hyperglycemia.

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