scholarly journals Prolactin-Releasing Peptide: Physiological and Pharmacological Properties

2019 ◽  
Vol 20 (21) ◽  
pp. 5297 ◽  
Author(s):  
Pražienková ◽  
Popelová ◽  
Kuneš ◽  
Maletínská
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Therapeutic Potential ◽  
Main Role ◽  
Pharmacological Properties ◽  
Physiological Functions ◽  
Structure Activity ◽  
C Terminus ◽  
Prolactin Releasing Peptide ◽  
G Protein Coupled

Prolactin-releasing peptide (PrRP) belongs to the large RF-amide neuropeptide family with a conserved Arg-Phe-amide motif at the C-terminus. PrRP plays a main role in the regulation of food intake and energy expenditure. This review focuses not only on the physiological functions of PrRP, but also on its pharmacological properties and the actions of its G-protein coupled receptor, GPR10. Special attention is paid to structure-activity relationship studies on PrRP and its analogs as well as to their effect on different physiological functions, mainly their anorexigenic and neuroprotective features and the regulation of the cardiovascular system, pain, and stress. Additionally, the therapeutic potential of this peptide and its analogs is explored.

scholarly journals GPR17 gene disruption does not alter food intake or glucose homeostasis in mice

2015 ◽  
Vol 112 (6) ◽  
pp. 1845-1849 ◽  
Author(s):  
Jason Mastaitis ◽  
Soo Min ◽  
Ralf Elvert ◽  
Aimo Kannt ◽  
Yurong Xin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Food Intake ◽  
Glucose Homeostasis ◽  
Gene Disruption ◽  
Therapeutic Potential ◽  
Intracerebroventricular Injection ◽  
Wild Type ◽  
Pharmacological Modulation ◽  
G Protein Coupled

G protein-coupled receptor 17 (GPR17) was recently reported to be a Foxo1 target in agouti-related peptide (AGRP) neurons. Intracerebroventricular injection of GPR17 agonists induced food intake, whereas administration of an antagonist to the receptor reduced feeding. These data lead to the conclusion that pharmacological modulation of GPR17 has therapeutic potential to treat obesity. Here we report that mice deficient in Gpr17 (Gpr17−/−) have similar food intake and body weight compared with their wild-type littermates. Gpr17−/− mice have normal hypothalamic Agrp mRNA expression, AGRP plasma levels, and metabolic rate. GPR17 deficiency in mice did not affect glucose homeostasis or prevent fat-induced insulin resistance. These data do not support a role for GPR17 in the control of food intake, body weight, or glycemic control.

scholarly journals Long-term effects of ghrelin and ghrelin receptor agonists on energy balance in rats

2008 ◽  
Vol 295 (1) ◽  
pp. E78-E84 ◽  
Author(s):  
Sabine Strassburg ◽  
Stefan D. Anker ◽  
Tamara R. Castaneda ◽  
Lukas Burget ◽  
Diego Perez-Tilve ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Therapeutic Potential ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Positive Energy ◽  
High Dose ◽  
Growth Hormone Secretagogue

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is the only circulating agent to powerfully promote a positive energy balance. Such action is mediated predominantly by central nervous system pathways controlling food intake, energy expenditure, and nutrient partitioning. The ghrelin pathway may therefore offer therapeutic potential for the treatment of catabolic states. However, the potency of the endogenous hormone ghrelin is limited due to a short half-life and the fragility of its bioactivity ensuring acylation at serine 3. Therefore, we tested the metabolic effects of two recently generated GHS-R agonists, BIM-28125 and BIM-28131, compared with ghrelin. All agents were administered continuously for 1 mo in doses of 50 and 500 nmol·kg−1·day−1 using implanted subcutaneous minipumps in rats. High-dose treatment with single agonists or ghrelin increased body weight gain by promoting fat mass, whereas BIM-28131 was the only one also increasing lean mass significantly. Food intake increased during treatment with BIM-28131 or ghrelin, whereas no effects on energy expenditure were detected. With the lower dose, only BIM-28131 had a significant effect on body weight. This also held true when the compound was administered by subcutaneous injection three times/day. No symptoms or signs of undesired effects were observed in any of the studies or treated groups. These results characterize BIM-28131 as a promising GHS-R agonist with an attractive action profile for the treatment of catabolic disease states such as cachexia.

scholarly journals Involvement of the Acyl-CoA binding domain containing 7 in the control of food intake and energy expenditure in mice

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Damien Lanfray ◽  
Alexandre Caron ◽  
Marie-Claude Roy ◽  
Mathieu Laplante ◽  
Fabrice Morin ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Arcuate Nucleus ◽  
Binding Domain ◽  
Nucleotide Polymorphism ◽  
Melanocortin System ◽  
Single Nucleotide ◽  
Hypothalamic Arcuate Nucleus ◽  
Paralog Gene ◽  
G Protein Coupled

Acyl-CoA binding domain-containing 7 (Acbd7) is a paralog gene of the diazepam-binding inhibitor/Acyl-CoA binding protein in which single nucleotide polymorphism has recently been associated with obesity in humans. In this report, we provide converging evidence indicating that a splice variant isoform of the Acbd7 mRNA is expressed and translated by some POMC and GABAergic-neurons in the hypothalamic arcuate nucleus (ARC). We have demonstrated that the ARC ACBD7 isoform was produced and processed into a bioactive peptide referred to as nonadecaneuropeptide (NDN) in response to catabolic signals. We have characterized NDN as a potent anorexigenic signal acting through an uncharacterized endozepine G protein-coupled receptor and subsequently via the melanocortin system. Our results suggest that ACBD7-producing neurons participate in the hypothalamic leptin signalling pathway. Taken together, these data suggest that ACBD7-producing neurons are involved in the hypothalamic control exerted on food intake and energy expenditure by the leptin-melanocortin pathway.

scholarly journals Recombinant and Chimeric Disintegrins in Preclinical Research

Toxins ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 321 ◽  
Author(s):  
Victor David ◽  
Barbara Barbosa Succar ◽  
João Alfredo de Moraes ◽  
Roberta Ferreira Gomes Saldanha-Gama ◽  
Christina Barja-Fidalgo ◽  
...  
Keyword(s):  
Tumor Metastasis ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Site Directed Mutagenesis ◽  
Integrin Receptors ◽  
Preclinical Research ◽  
Structure Activity ◽  
C Terminus ◽  
Phylogenetic Origin ◽  
Chimeric Peptides

Disintegrins are a family of small cysteine-rich peptides, found in a wide variety of snake venoms of different phylogenetic origin. These peptides selectively bind to integrins, which are heterodimeric adhesion receptors that play a fundamental role in the regulation of many physiological and pathological processes, such as hemostasis and tumor metastasis. Most disintegrins interact with integrins through the RGD (Arg-Gly-Asp) sequence loop, resulting in an active site that modulates the integrin activity. Some variations in the tripeptide sequence and the variability in its neighborhood result in a different specificity or affinity toward integrin receptors from platelets, tumor cells or neutrophils. Recombinant forms of these proteins are obtained mainly through Escherichia coli, which is the most common host used for heterologous expression. Advances in the study of the structure-activity relationship and importance of some regions of the molecule, especially the hairpin loop and the C-terminus, rely on approaches such as site-directed mutagenesis and the design and expression of chimeric peptides. This review provides highlights of the biological relevance and contribution of recombinant disintegrins to the understanding of their binding specificity, biological activities and therapeutic potential. The biological and pharmacological relevance on the newest discoveries about this family of integrin-binding proteins are discussed.

A compendium of G-protein–coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure

2020 ◽  
Vol 134 (5) ◽  
pp. 473-512 ◽  
Author(s):  
Ryan P. Ceddia ◽  
Sheila Collins
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Signaling Pathways ◽  
G Protein ◽  
Uncoupling Protein ◽  
Beige Adipocytes ◽  
Nucleotide Regulation ◽  
Ucp1 Expression ◽  
Thermogenic Adipocytes ◽  
G Protein Coupled

Abstract With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand–receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein–coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.

Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors

2019 ◽  
Vol 25 (26) ◽  
pp. 2892-2905 ◽  
Author(s):  
Sumit Jamwal ◽  
Ashish Mittal ◽  
Puneet Kumar ◽  
Dana M. Alhayani ◽  
Amal Al-Aboudi
Keyword(s):  
Nervous System ◽  
Therapeutic Potential ◽  
The Body ◽  
Membrane Receptors ◽  
Physiological Importance ◽  
Physiological Processes ◽  
Central Nervous Systems ◽  
Energy Consuming ◽  
Metabolic Dysfunctions ◽  
G Protein Coupled

Adenosine is a naturally occurring nucleoside and an essential component of the energy production and utilization systems of the body. Adenosine is formed by the degradation of adenosine-triphosphate (ATP) during energy-consuming processes. Adenosine regulates numerous physiological processes through activation of four subtypes of G-protein coupled membrane receptors viz. A1, A2A, A2B and A3. Its physiological importance depends on the affinity of these receptors and the extracellular concentrations reached. ATP acts as a neurotransmitter in both peripheral and central nervous systems. In the peripheral nervous system, ATP is involved in chemical transmission in sensory and autonomic ganglia, whereas in central nervous system, ATP, released from synaptic terminals, induces fast excitatory postsynaptic currents. ATP provides the energetics for all muscle movements, heart beats, nerve signals and chemical reactions inside the body. Adenosine has been traditionally considered an inhibitor of neuronal activity and a regulator of cerebral blood flow. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosinerelated drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases. This review will summarize the therapeutic potential and recent SAR and pharmacology of adenosine and its receptor agonists and antagonists.

The Therapeutic Potential of Purinergic Receptors in Alzheimer’s Disease and Promising Therapeutic Modulators

2020 ◽  
Vol 20 ◽  
Author(s):  
Lili Pan ◽  
Yu Ma ◽  
Yunchun Li ◽  
Haoxing Wu ◽  
Rui Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Purinergic Receptors ◽  
Therapeutic Potential ◽  
Purinergic Signaling ◽  
Memory Loss ◽  
Related Research ◽  
Central Nervous System Disorders ◽  
G Protein Coupled

Abstract:: Recent studies have proven that the purinergic signaling pathway plays a key role in neurotransmission and neuromodulation, and is involved in various neurodegenerative diseases and psychiatric disorders. With the characterization of the subtypes of receptors in purinergic signaling, i.e. the P1 (adenosine), P2X (ion channel) and P2Y (G protein-coupled), more attentions were paid to the pathophysiology and therapeutic potential of purinergic signaling in central nervous system disorders. Alzheimer’s disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. However, as drug development aimed to prevent or control AD follows a series of failures in recent years, more researchers focused on the neuroprotection-related mechanisms such as purinergic signaling in AD patients to find a potential cure. This article reviews the recent discoveries of purinergic signaling in AD, summaries the potential agents as modulators for the receptors of purinergic signaling in AD related research and treatments. Thus, our paper provided an insight for purinergic signaling in the development of anti-AD therapies.

Exploring the Chemistry and Therapeutic Potential of Triazoles: A Comprehensive Literature Review

2019 ◽  
Vol 19 (16) ◽  
pp. 1298-1368 ◽  
Author(s):  
Ankit Jain ◽  
Poonam Piplani
Keyword(s):  
Oxidative Stress ◽  
Drug Discovery ◽  
Literature Review ◽  
Structural Modification ◽  
Therapeutic Potential ◽  
Pharmacological Properties ◽  
Pharmacological Activities ◽  
Triazole Derivatives ◽  
Comprehensive Literature Review ◽  
The Common

: Triazole is a valuable platform in medicinal chemistry, possessing assorted pharmacological properties, which could play a major role in the common mechanisms associated with various disorders like cancer, infections, inflammation, convulsions, oxidative stress and neurodegeneration. Structural modification of this scaffold could be helpful in the generation of new therapeutically useful agents. Although research endeavors are moving towards the growth of synthetic analogs of triazole, there is still a lot of scope to achieve drug discovery break-through in this area. Upcoming therapeutic prospective of this moiety has captured the attention of medicinal chemists to synthesize novel triazole derivatives. The authors amalgamated the chemistry, synthetic strategies and detailed pharmacological activities of the triazole nucleus in the present review. Information regarding the marketed triazole derivatives has also been incorporated. The objective of the review is to provide insights to designing and synthesizing novel triazole derivatives with advanced and unexplored pharmacological implications.

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