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https://www.readbyqxmd.com/read/28630289/green-mamba-peptide-targets-type-2-vasopressin-receptor-against-polycystic-kidney-disease
#1
Justyna Ciolek, Helen Reinfrank, Loïc Quinton, Say Viengchareun, Enrico A Stura, Laura Vera, Sabrina Sigismeau, Bernard Mouillac, Hélène Orcel, Steve Peigneur, Jan Tytgat, Laura Droctové, Fabrice Beau, Jerome Nevoux, Marc Lombès, Gilles Mourier, Edwin De Pauw, Denis Servent, Christiane Mendre, Ralph Witzgall, Nicolas Gilles
Polycystic kidney diseases (PKDs) are genetic disorders that can cause renal failure and death in children and adults. Lowering cAMP in cystic tissues through the inhibition of the type-2 vasopressin receptor (V2R) constitutes a validated strategy to reduce disease progression. We identified a peptide from green mamba venom that exhibits nanomolar affinity for the V2R without any activity on 155 other G-protein-coupled receptors or on 15 ionic channels. Mambaquaretin-1 is a full antagonist of the V2R activation pathways studied: cAMP production, beta-arrestin interaction, and MAP kinase activity...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28577072/regulation-of-renal-na-k-cl-cotransporters-by-vasopressin
#2
REVIEW
Sebastian Bachmann, Kerim Mutig
Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption...
June 2, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28458780/identification-of-olfactory-receptor-genes-in-the-japanese-grenadier-anchovy-coilia-nasus
#3
Guoli Zhu, Liangjiang Wang, Wenqiao Tang, Xiaomei Wang, Cong Wang
Olfaction is essential for fish to detect odorant elements in the environment and plays a critical role in navigating, locating food and detecting predators. Olfactory function is produced by the olfactory transduction pathway and is activated by olfactory receptors (ORs) through the binding of odorant elements. Recently, four types of olfactory receptors have been identified in vertebrate olfactory epithelium, including main odorant receptors (MORs), vomeronasal type receptors (VRs), trace-amine associated receptors (TAARs) and formyl peptide receptors (FPRs)...
2017: Genes & Genomics
https://www.readbyqxmd.com/read/28455745/expanding-the-role-of-vasopressin-antagonism-in-polycystic-kidney-diseases-from-adults-to-children
#4
Peter Janssens, Caroline Weydert, Stephanie De Rechter, Karl Martin Wissing, Max Christoph Liebau, Djalila Mekahli
Polycystic kidney disease (PKD) encompasses a group of genetic disorders that are common causes of renal failure. The two classic forms of PKD are autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD). Despite their clinical differences, ARPKD and ADPKD share many similarities. Altered intracellular Ca(2+) and increased cyclic adenosine monophosphate (cAMP) concentrations have repetitively been described as central anomalies that may alter signaling pathways leading to cyst formation...
April 28, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28419717/ligand-recognition-properties-of-the-vasopressin-v2-receptor-studied-under-qsar-and-molecular-modeling-strategies
#5
Marlet Martínez-Archundia, Brenda Colín-Astudillo, L M Moreno-Vargas, G Ramírez-Galicia, R Garduño-Juárez, O Deeb, Martha C Contreras-Romo, A Quintanar-Stephano, Edgar Abarca-Rojano, José Correa-Basurto
The design of new drugs that target vasopressin 2 receptor (V2R) is of vital importance to develop new therapeutic alternatives to treat diseases such as heart failure, polycystic kidney disease, etc. To get structural insights related to V2R-ligand recognition, we have used a combined approach of docking, molecular dynamics simulations (MD) and quantitative structure-activity relationship (QSAR) to elucidate the detailed interaction of the V2R with 119 of its antagonists. The three-dimensional model of V2R was built by threading methods refining its structure through MD simulations upon which the 119 ligands were subjected to docking studies...
April 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28416805/a-new-inhibitor-of-the-%C3%AE-arrestin-ap2-endocytic-complex-reveals-interplay-between-gpcr-internalization-and-signalling
#6
Alexandre Beautrait, Justine S Paradis, Brandon Zimmerman, Jenna Giubilaro, Ljiljana Nikolajev, Sylvain Armando, Hiroyuki Kobayashi, Lama Yamani, Yoon Namkung, Franziska M Heydenreich, Etienne Khoury, Martin Audet, Philippe P Roux, Dmitry B Veprintsev, Stéphane A Laporte, Michel Bouvier
In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28412033/antagonism-of-vasopressin-v2-receptor-improves-albuminuria-at-the-early-stage-of-diabetic-nephropathy-in-a-mouse-model-of-type-2-diabetes
#7
Ray El Boustany, Christopher Taveau, Catherine Chollet, Gilberto Velho, Lise Bankir, François Alhenc-Gelas, Ronan Roussel, Nadine Bouby
AIMS: Vasopressin is increased in diabetes and was shown to contribute to development of diabetic nephropathy through V2 receptor (V2R) activation in an experimental model of type 1 diabetes. The role of V2R in type 2 diabetes remains undocumented. This study addresses the issue in a mouse model of type 2 diabetes. METHODS: Male obese diabetic db/db mice were treated for 12weeks with a selective V2R antagonist (SR121463) and compared to non-treated db/db and non-diabetic db/m mice...
June 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28381458/protein-phosphatase-2c-pp2c-is-responsible-for-vp-induced-dephosphorylation-of-aqp2-serine-261
#8
Pui W Cheung, Lars Ueberdiek, Jack Day, Richard Bouley, Dennis Brown
AQP2 trafficking is regulated by phosphorylation and dephosphorylation of serine residues in the AQP2 c-terminus. Vasopressin (VP) binding to its receptor (V2R) leads to a cascade of events that result in the phosphorylation of serine 256 (S256), S264 and S269, but dephosphorylation of S261. To identify which phosphatase is responsible for VP-induced S261 dephosphorylation, we pretreated cells with different phosphatase inhibitors before VP stimulation. Only sanguinarine, a specific protein phosphatase 2C (PP2C) inhibitor, abolished VP-induced S261 dephosphorylation, but not inhibitors of PP1, PP2A (okadaic acid) or PP2B (cyclosporine)...
April 5, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28326667/the-v2-receptor-antagonist-tolvaptan-raises-cytosolic-calcium-and-prevents-aqp2-trafficking-and-function-an-in-vitro-and-in-vivo-assessment
#9
Grazia Tamma, Annarita Di Mise, Marianna Ranieri, Ari Geller, Roberto Tamma, Alberta Zallone, Giovanna Valenti
Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin-regulated water reabsorption via aquaporin-2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2-mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin-cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney...
March 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28258576/diabetes-insipidus
#10
H A Jenny Lu
Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understand the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI ) ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28228552/core-engagement-with-%C3%AE-arrestin-is-dispensable-for-agonist-induced-vasopressin-receptor-endocytosis-and-erk-activation
#11
Punita Kumari, Ashish Srivastava, Eshan Ghosh, Ravi Ranjan, Shalini Dogra, Prem N Yadav, Arun K Shukla
G protein-coupled receptors (GPCRs) exhibit highly conserved activation and signaling mechanisms by which agonist stimulation leads to coupling of heterotrimeric G proteins and generation of second messenger response. This is followed by receptor phosphorylation, primarily in the carboxyl terminus but also in the cytoplasmic loops, and subsequent binding of arrestins. GPCRs typically recruit arrestins through two different sets of interactions, one involving phosphorylated receptor tail and the other mediated by the receptor core...
April 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28194370/peptide-agonists-of-vasopressin-v2-receptor-reduce-expression-of-neuroendocrine-markers-and-tumor-growth-in-human-lung-and-prostate-tumor-cells
#12
Marina Pifano, Juan Garona, Carla S Capobianco, Nazareno Gonzalez, Daniel F Alonso, Giselle V Ripoll
Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28192441/cyclic-amp-regulates-postnatal-development-of-neural-and-behavioral-responses-to-nacl-in-rats
#13
Jie Qian, Shobha Mummalaneni, Tam-Hao T Phan, Gerard L Heck, John A DeSimone, David West, Sunila Mahavadi, Deanna Hojati, Karnam S Murthy, Mee-Ra Rhyu, Andrew I Spielman, Mehmet Hakan Özdener, Vijay Lyall
During postnatal development rats demonstrate an age-dependent increase in NaCl chorda tympani (CT) responses and the number of functional apical amiloride-sensitive epithelial Na+ channels (ENaCs) in salt sensing fungiform (FF) taste receptor cells (TRCs). Currently, the intracellular signals that regulate the postnatal development of salt taste have not been identified. We investigated the effect of cAMP, a downstream signal for arginine vasopressin (AVP) action, on the postnatal development of NaCl responses in 19-23 day old rats...
2017: PloS One
https://www.readbyqxmd.com/read/28179252/aquaporin-2-membrane-targeting-still-a-conundrum
#14
Emma Tina Bisgaard Olesen, Robert A Fenton
The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis. In this brief review we assess the role of cyclic adenosine monophosphate (cAMP) and discuss the emerging concept that V2R-mediated AQP2 trafficking is cAMP-independent.
February 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28145450/development-of-a-human-vasopressin-v1a-receptor-antagonist-from-an-evolutionary-related-insect-neuropeptide
#15
Maria Giulia Di Giglio, Markus Muttenthaler, Kasper Harpsøe, Zita Liutkeviciute, Peter Keov, Thomas Eder, Thomas Rattei, Sarah Arrowsmith, Susan Wray, Ales Marek, Tomas Elbert, Paul F Alewood, David E Gloriam, Christian W Gruber
Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28116432/-partial-recovery-of-thermal-sensory-functions-in-skeletal-class-%C3%A2-patients-undergoing-orthognathic-surgery
#16
Xin-Yu Gu, Jing-Lu Zhang, Dong Lv, Wen-Jing Chen
PURPOSE: To clarify whether trigeminal somatosensory function will be changed after orthodontic treatment as well as after orthognathic surgery. METHODS: A series of 20 patients with a mean age of 20.9±1.74 years were recruited. Thermal quantitative sensory tests were conducted before orthodontic treatment (T0), before orthognathic surgery (T1), 2 months after orthognathic surgery (T2), and 6 months after orthognathic surgery (T3). The cold detection threshold (CDT), cold pain threshold (CPT), warm detection threshold (WDT) and heat pain threshold (HPT) were determined...
October 2016: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
https://www.readbyqxmd.com/read/28074292/reliability-of-the-nociceptive-blink-reflex-evoked-by-electrical-stimulation-of-the-trigeminal-nerve-in-humans
#17
Yuri Martins Costa, Lene Baad-Hansen, Leonardo Rigoldi Bonjardim, Paulo César Rodrigues Conti, Peter Svensson
OBJECTIVE: The nociceptive blink reflex (nBR) can be useful to investigate trigeminal nociceptive function. The aim of this study was to estimate the reliability of the nBR evoked by electrical stimulation of the three branches of the trigeminal nerve under the following conditions: over time (test-retest and intrarater reliability) and by two examiners (interrater reliability). MATERIALS AND METHODS: Twenty-one healthy participants were evaluated in two sessions (24 h apart)...
January 10, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/27990576/coordinated-shift-of-olfactory-amino-acid-responses-and-v2r-expression-to-an-amphibian-water-nose-during-metamorphosis
#18
Adnan S Syed, Alfredo Sansone, Thomas Hassenklöver, Ivan Manzini, Sigrun I Korsching
All olfactory receptors identified in teleost fish are expressed in a single sensory surface, whereas mammalian olfactory receptor gene families segregate into different olfactory organs, chief among them the main olfactory epithelium expressing ORs and TAARs, and the vomeronasal organ expressing V1Rs and V2Rs. A transitional stage is embodied by amphibians, with their vomeronasal organ expressing more 'modern', later diverging V2Rs, whereas more 'ancient', earlier diverging V2Rs are expressed in the main olfactory epithelium...
December 18, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27912243/vomeronasal-receptors-in-vertebrates-and-the-evolution-of-pheromone-detection
#19
Liliana Silva, Agostinho Antunes
Pheromones were identified as chemical signals used for intraspecific communication in insects (e.g., sexual attraction) in the 1950s. However, only almost 40 years later the vomeronasal receptors type-1 (V1R) and type-2 (V2R) were identified, usually associated with the presence of a vomeronasal organ (VNO). VRs are widespread in amphibians, reptiles, and mammals, but birds lost the VNO. Similarly, fishes lack VRs and a VNO but can still detect pheromones, instead using the olfactory receptors related to class A and class C G protein-coupled receptors...
February 8, 2017: Annual Review of Animal Biosciences
https://www.readbyqxmd.com/read/27689822/transcriptomic-profiles-of-the-upper-olfactory-rosette-in-cultured-and-wild-senegalese-sole-solea-senegalensis-males
#20
E Fatsini, R Bautista, M Manchado, N J Duncan
The aims of this study were the characterization of the upper olfactory epithelium of cultured and wild Senegalese sole mature males at histological and transcriptomic (using RNA-Seq) level. No significant differences in tissue structure, cell types and cellular distribution pattern (olfactory sensory neurons) were identified between cultured and wild specimens. Deep transcriptomic analysis showed 2387 transcripts were differentially expressed between cultured and wild groups. A detailed analysis identified the differentially expressed transcripts included some olfactory receptors (OR, TAAR and V2R-like) and transcripts related with the control of reproduction such as the brain aromatase cytochrome P450 and tachykinin-3...
December 2016: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
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