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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
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
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)...
September 7, 2016: Journal of Radiation Research
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 GPCR genes, including V2 vasopressin receptor (V2R) gene, often cause misfolded receptors, leading to the 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. Although non-peptide V2R antagonists have been shown to rescue the membrane localization of V2R mutants, their level of functional rescue is weak...
September 6, 2016: Journal of Biological Chemistry
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
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...
August 17, 2016: American Journal of Physiology. Renal Physiology
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
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
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
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
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
Juan Garona, Marina Pifano, Maria B Pastrian, Daniel E Gomez, Giselle V Ripoll, Daniel F Alonso
[V(4)Q(5)]dDAVP is a novel 2nd generation vasopressin analogue with robust antitumour activity against metastatic breast cancer. We recently reported that, by acting on vasopressin V2r membrane receptor present in tumour cells and microvascular endothelium, [V(4)Q(5)]dDAVP inhibits angiogenesis and metastatic progression of the disease without overt toxicity. Despite chemotherapy remaining as a primary therapeutic option for aggressive breast cancer, its use is limited by low selectivity and associated adverse effects...
August 2016: Clinical & Experimental Metastasis
Lu Xing, Rikke Nørregaard
BACKGROUND: The ability of the immature kidney to concentrate urine is lower than in adults. The aquaporin (AQP) family and the vasopressin V2 receptor (V2R) play a critical role in the urinary concentrating capacity. Here we investigated a possible sex difference in AQP1, AQP2, AQP3, and AQP4 as well as V2R expression in the fetal pig kidney at different gestation stages. METHODS: Pig fetuses were divided into three groups according to gestation age of 60, 80, and 100 d...
September 2016: Pediatric Research
Daniela Biechl, Kristin Tietje, Gabriele Gerlach, Mario F Wullimann
Zebrafish larvae imprint on visual and olfactory kin cues at day 5 and 6 postfertilization, respectively, resulting in kin recognition later in life. Exposure to non-kin cues prevents imprinting and kin recognition. Imprinting depends on MHC class II related signals and only larvae sharing MHC class II alleles can imprint on each other. Here, we analyzed which type of olfactory sensory neuron (OSN) detects kin odor. The single teleost olfactory epithelium harbors ciliated OSNs carrying OR and TAAR gene family receptors (mammals: main olfactory epithelium) and microvillous OSNs with V1R and V2R gene family receptors (mammals: vomeronasal organ)...
2016: Scientific Reports
Yoshihisa Sakurai, Zenya Fujita, Yusuke Ishige
This study aims to develop and validate an automated system for identifying skating-style cross-country subtechniques using inertial sensors. In the first experiment, the performance of a male cross-country skier was used to develop an automated identification system. In the second, eight male and seven female college cross-country skiers participated to validate the developed identification system. Each subject wore inertial sensors on both wrists and both roller skis, and a small video camera on a backpack...
2016: Sensors
Rachel Lord, Keith George, John Somauroo, Nikhil Jain, Kristin Reese, Martin D Hoffman, Francois Haddad, Euan Ashley, Helen Jones, David Oxborough
BACKGROUND: Prolonged strenuous exercise has a profound effect on cardiac function. The right heart may be more susceptible to this imposition; yet, right-sided chest leads have not been utilised in this setting. METHODS: Thirty highly trained athletes at the 2014 Western States 100-mile Endurance Run from Squaw Valley to Auburn, California (body mass 68 ± 12 kg, age 45 ± 10 years, 57 ± 15 miles per week) were recruited for the study. Pre- and post-race, a right-sided 12-lead ECG was obtained and data were extracted for P, R and S waves, J point, ST segment and T wave amplitude...
November 2016: European Journal of Sport Science
Janet D Klein, Yanhua Wang, Mitsi A Blount, Patrick A Molina, Lauren M LaRocque, Joseph A Ruiz, Jeff M Sands
Nephrogenic diabetes insipidus (NDI) is characterized by production of very large quantities of dilute urine due to an inability of the kidney to respond to vasopressin. Congenital NDI results from mutations in the type 2 vasopressin receptor (V2R) in ∼90% of families. These patients do not have mutations in aquaporin-2 (AQP2) or urea transporter UT-A1 (UT-A1). We tested adenosine monophosphate kinase (AMPK) since it is known to phosphorylate another vasopressin-sensitive transporter, NKCC2 (Na-K-2Cl cotransporter)...
May 15, 2016: American Journal of Physiology. Renal Physiology
Itaru Goto, Kaoru Dohi, Yoshito Ogihara, Ryuji Okamoto, Norikazu Yamada, Yoshihide Mitani, Masaaki Ito
BACKGROUND: The expression of vasopressin type 2 receptor (V2R) in the lung, and the long-term effects of tolvaptan, a selective V2R antagonist, on pulmonary circulation and right ventricular (RV) remodeling in a pulmonary arterial hypertension (PAH) rat model were evaluated. METHODS AND RESULTS: Six-week-old male Sprague-Dawley rats were injected subcutaneously with 20 mg/kg of SU5416 and were exposed to hypoxia for 3 weeks followed by re-exposure to normoxia for 7 weeks...
2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Wolfgang E Kühn, Gerd Walz
BACKGROUND: About one in 2000 persons in Europe suffers from autosomal dominant polycystic kidney disease (ADPKD). The treatment of this disease up to the present has been limited to the management of complications. METHODS: This review is based on pertinent publications, mostly of the last three years, that were retrieved by a selective search in PubMed. RESULTS: Kidney volume is probably the most important predictive factor for the loss of renal function...
December 21, 2015: Deutsches Ärzteblatt International
Steven M Foord
Heterodimerization enhances the complexity of ligand recognition and diversity of signaling responses of heterotrimeric guanine nucleotide-binding protein-coupled receptors (GPCRs). Many accessory proteins (for ion channels or GPCRs) appear to associate with their partners relatively early in the process whereby proteins are transported to the cell surface; their roles in modulating function may have evolved out of simple proximity to a protein that once upon a time they either facilitated or accompanied through the maturation process...
July 8, 2003: Science's STKE: Signal Transduction Knowledge Environment
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