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https://www.readbyqxmd.com/read/28228552/core-engagement-with-%C3%AE-arrestin-is-dispensable-for-agonist-induced-vasopressin-receptor-endocytosis-and-erk-activation
#1
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 where 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 set of interactions, one involving phosphorylated receptor tail and the other mediated by the receptor core...
February 22, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
September 20, 2016: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/27684435/in-depth-physiological-analysis-of-defined-cell-populations-in-acute-tissue-slices-of-the-mouse-vomeronasal-organ
#11
Tobias Ackels, Daniela R Drose, Marc Spehr
In most mammals, the vomeronasal organ (VNO) is a chemosensory structure that detects both hetero- and conspecific social cues. Vomeronasal sensory neurons (VSNs) express a specific type of G protein-coupled receptor (GPCR) from at least three different chemoreceptor gene families allowing sensitive and specific detection of chemosensory cues. These families comprise the V1r and V2r gene families as well as the formyl peptide receptor (FPR)-related sequence (Fpr-rs) family of putative chemoreceptor genes. In order to understand the physiology of vomeronasal receptor-ligand interactions and downstream signaling, it is essential to identify the biophysical properties inherent to each specific class of VSNs...
2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27605630/dosimetric-impact-of-an-air-passage-on-intraluminal-brachytherapy-for-bronchus-cancer
#12
Hiroyuki Okamoto, Akihisa Wakita, Satoshi Nakamura, Shie Nishioka, Ako Aikawa, Toru Kato, Yoshihisa Abe, Kazuma Kobayashi, Koji Inaba, Naoya Murakami, Jun Itami
The brachytherapy dose calculations used in treatment planning systems (TPSs) have conventionally been performed assuming homogeneous water. Using measurements and a Monte Carlo simulation, we evaluated the dosimetric impact of an air passage on brachytherapy for bronchus cancer. To obtain the geometrical characteristics of an air passage, we analyzed the anatomical information from CT images of patients who underwent intraluminal brachytherapy using a high-dose-rate (192)Ir source (MicroSelectron V2r®, Nucletron)...
November 2016: Journal of Radiation Research
https://www.readbyqxmd.com/read/27601473/analysis-of-the-v2-vasopressin-receptor-v2r-mutations-causing-partial-nephrogenic-diabetes-insipidus-highlights-a-sustainable-signaling-by-a-non-peptide-v2r-agonist
#13
Noriko Makita, Tomohiko Sato, Yuki Yajima-Shoji, Junichiro Sato, Katsunori Manaka, Makiko Eda-Hashimoto, Masanori Ootaki, Naoki Matsumoto, Masaomi Nangaku, Taroh Iiri
Disease-causing mutations in G protein-coupled receptor (GPCR) genes, including the V2 vasopressin receptor (V2R) gene, often cause misfolded receptors, leading to a defect in plasma membrane trafficking. A novel V2R mutation, T273M, identified in a boy with partial nephrogenic diabetes insipidus (NDI), shows intracellular localization and partial defects similar to the two mutants we described previously (10). Although non-peptide V2R antagonists have been shown to rescue the membrane localization of V2R mutants, their level of functional rescue is weak...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27558562/the-vasopressin-type-2-receptor-and-prostaglandin-receptors-ep2-and-ep4-can-increase-aquaporin-2-plasma-membrane-targeting-through-a-camp-independent-pathway
#14
Emma Tina Bisgaard Olesen, Hanne Bjerregaard Moeller, Mette Assentoft, Nanna MacAulay, Robert A Fenton
Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be cAMP-dependent. However, on the basis of recent reports, it was hypothesized in the current study that increased cAMP levels are not necessary for AQP2 membrane targeting. The role and dynamics of cAMP signaling on AQP2 membrane targeting in Madin-Darby Canine Kidney and mouse cortical collecting duct (mpkCCD14) cells was examined using selective agonists against the V2R (dDAVP), EP2 (butaprost) and EP4 (CAY10580)...
August 24, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27534996/physiological-insights-into-novel-therapies-for-nephrogenic-diabetes-insipidus
#15
Jeff M Sands, Janet D Klein
Fundamental kidney physiology research can provide important insight into how the kidney works and suggest novel therapeutic opportunities to treat human diseases. This is especially true for nephrogenic diabetes insipidus (NDI). Over the past decade, studies elucidating the molecular physiology and signaling pathways regulating water transport have suggested novel therapeutic possibilities. In patients with congenital NDI due to mutations in the type 2 vasopressin receptor (V2R) or acquired NDI due to lithium (or other medications), there are no functional abnormalities in the aquaporin-2 (AQP2) water channel, or in another key inner medullary transport protein, the UT-A1 urea transporter...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27478876/metformin-improves-urine-concentration-in-rodents-with-nephrogenic-diabetes-insipidus
#16
Orhan Efe, Janet D Klein, Lauren M LaRocque, Huiwen Ren, Jeff M Sands
Urine concentration is regulated by vasopressin. Congenital nephrogenic diabetes insipidus (NDI) is caused by vasopressin type 2 receptor (V2R) mutations. We studied whether metformin could improve urine concentration in rodent models of congenital NDI by stimulating AMPK. To block the V2R in rats, tolvaptan (10 mg/kg/d) was given by oral gavage with or without metformin (800 mg/ kg/d). Control rats received vehicle with or without metformin. Tamoxifen-induced V2R KO mice were given metformin (600 mg/kg) or vehicle twice daily...
July 21, 2016: JCI Insight
https://www.readbyqxmd.com/read/27389877/receptor-antagonism-agonism-can-be-uncoupled-from-pharmacoperone-activity
#17
Jo Ann Janovick, Timothy P Spicer, Emery Smith, Thomas D Bannister, Terry Kenakin, Louis Scampavia, P Michael Conn
Pharmacoperones rescue misrouted mutants of the vasopressin receptor type 2 (V2R) and enable them to traffic to the correct biological locus where they function. Previously, a library of nearly 645,000 structures was interrogated with a high throughput screen; pharmacoperones were identified for V2R mutants with a view toward correcting the underlying mutational defects in nephrogenic diabetes insipidus. In the present study, an orthologous assay was used to evaluate hits from the earlier study. We found no consistent relation between antagonism or agonism and pharmacoperone activity...
October 15, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27355191/mutations-of-vasopressin-receptor-2-including-novel-l312s-have-differential-effects-on-trafficking
#18
Anatoly Tiulpakov, Carl W White, Rekhati S Abhayawardana, Heng B See, Audrey S Chan, Ruth M Seeber, Julian I Heng, Ivan Dedov, Nathan J Pavlos, Kevin D G Pfleger
Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a genetic disease first described in 2 unrelated male infants with severe symptomatic hyponatremia. Despite undetectable arginine vasopressin levels, patients have inappropriately concentrated urine resulting in hyponatremia, hypoosmolality, and natriuresis. Here, we describe and functionally characterize a novel vasopressin type 2 receptor (V2R) gain-of-function mutation. An L312S substitution in the seventh transmembrane domain was identified in a boy presenting with water-induced hyponatremic seizures at the age of 5...
August 2016: Molecular Endocrinology
https://www.readbyqxmd.com/read/27306979/demonstration-of-the-functional-impact-of-vasopressin-signaling-in-the-thick-ascending-limb-by-a-targeted-transgenic-rat-approach
#19
Kerim Mutig, Tordis Borowski, Christin Boldt, Aljona Borschewski, Alexander Paliege, Elena Popova, Michael Bader, Sebastian Bachmann
The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by vasopressin 2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI), which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts. Previous work also suggested the AVP-V2R-mediated activation of Na(+)-K(+)-2Cl(-)-cotransporters (NKCC2) along the thick ascending limb (TAL) in the context of urine concentration, but its individual contribution to NDI or, more generally, to overall renal function was unclear...
August 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27280550/identification-of-potential-pharmacoperones-capable-of-rescuing-the-functionality-of-misfolded-vasopressin-2-receptor-involved-in-nephrogenic-diabetes-insipidus
#20
Emery Smith, Jo Ann Janovick, Thomas D Bannister, Justin Shumate, Louis Scampavia, P Michael Conn, Timothy P Spicer
Pharmacoperones correct the folding of otherwise misfolded protein mutants, restoring function (i.e., providing "rescue") by correcting their trafficking. Currently, most pharmacoperones possess intrinsic antagonist activity because they were identified using methods initially aimed at discovering such functions. Here, we describe an ultra-high-throughput homogeneous cell-based assay with a cAMP detection system, a method specifically designed to identify pharmacoperones of the vasopressin type 2 receptor (V2R), a GPCR that, when mutated, is associated with nephrogenic diabetes insipidus...
September 2016: Journal of Biomolecular Screening
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