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https://www.readbyqxmd.com/read/29351457/important-role-of-endothelium-dependent-hyperpolarization-in-pulmonary-microcirculation-in-male-mice-implications-for-hypoxia-induced-pulmonary-hypertension
#1
Shuhei Tanaka, Takashi Shiroto, Shigeo Godo, Hiroki Saito, Yosuke Ikumi, Akiyo Ito, Shoko Kajitani, Saori Sato, Hiroaki Shimokawa
Endothelium-dependent hyperpolarization (EDH) plays important roles in systemic circulation, whereas its role in pulmonary circulation remains largely unknown. Furthermore, the underlying mechanisms of pulmonary hypertension (PH) also remain to be elucidated. We thus aimed to elucidate the role of EDH in pulmonary circulation in general and in PH in particular. In isolated perfused lung using male wild-type mice, endothelium-dependent relaxations to bradykinin (BK) were significantly reduced in the presence of Nω-nitro-L-arginine (L-NNA) by ~50% as compared with those in the presence of indomethacin, and the combination of apamin plus charybdotoxin abolished the residual relaxations, showing the comparable contributions of nitric oxide (NO) and EDH in pulmonary microcirculation under physiological conditions...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351450/cardiac-vanilloid-receptor-1-afferent-depletion-enhances-stellate-ganglion-neuronal-activity-and-efferent-sympathetic-response-to-cardiac-stress
#2
Koji Yoshie, Pradeep S Rajendran, Louis Massoud, OhJin Kwon, Vasudev Tadimeti, Siamak Salavatian, Jeffrey Laurence Ardell, Kalyanam Shivkumar, Olujimi A Ajijola
Afferent fibers expressing the vanilloid receptor 1 (VR1) channel are implicated in cardiac nociception, however, their role in modulating reflex responses to cardiac stress is not well-understood. We evaluated this role in Yorkshire pigs by percutaneous epicardial application of resiniferatoxin (RTX), a toxic activator of the VR1 channel, resulting in depletion of cardiac VR1-expressing afferents. Hemodynamics, epicardial activation recovery intervals (ARIs), and in vivo activity of stellate ganglion (SG) neurons (SGNs) were recorded in control and RTX-treated animals...
January 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351301/investigation-of-the-proton-relay-system-operative-in-human-cystosolic-aminopeptidase-p
#3
Hui-Chuan Chang, Camy C-H Kung, Tzu-Ting Chang, Shu-Chuan Jao, Yu-Ting Hsu, Wen-Shan Li
Aminopeptidase P, a metalloprotease, targets Xaa-Proline peptides for cleavage [1-4]. There are two forms of human AMPP, a membrane-bound form (hmAMPP) and a soluble cytosolic form (hcAMPP)[5]. Similar to the angiotensin-I-converting enzyme, AMPP plays an important role in the catabolism of inflammatory and vasoactive peptides, known as kinins. The plasma kinin, bradykinin, was used as the substrate to conduct enzymatic activity analyses and to determine the Michaelis constant (Km) of 174 μM and the catalytic rate constant (kcat) of 10...
2018: PloS One
https://www.readbyqxmd.com/read/29337221/venom-characterization-of-the-amazonian-scorpion-tityus-metuendus
#4
C V F Batista, J G Martins, R Restano-Cassulini, F I V Coronas, F Z Zamudio, R Procópio, L D Possani
The soluble venom from the scorpion Tityus metuendus was characterized by various methods. In vivo experiments with mice showed that it is lethal. Extended electrophysiological recordings using seven sub-types of human voltage gated sodium channels (hNav1.1 to 1.7) showed that it contains both α- and β-scorpion toxin types. Fingerprint analysis by mass spectrometry identified over 200 distinct molecular mass components. At least 60 sub-fractions were recovered from HPLC separation. Five purified peptides were sequenced by Edman degradation, and their complete primary structures were determined...
January 11, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29334504/bradykinin-receptors-gene-expression-in-white-adipose-tissue-in-nondiabetic-patients-with-coronary-artery-disease
#5
Maria E Marketou, George Kochiadakis, Joanna Kontaraki, Evangelos Zacharis, Emmanouel Kanoupakis, Emmanouel Kallergis, Hercules Mavrakis, Panagiotis Tsiverdis, Dimitris Lempidakis, John Konstantinou, Konstantinos Fragkiadakis, Gregory Chlouverakis, Panos Vardas, Fragiskos Parthenakis
OBJECTIVES: Adipose tissue plays a key role in cardiovascular physiology. Kinin receptors are important determinant of the effect of adiposity on endothelial function and cardiovascular function. We examined the gene expression levels of kinin receptors in the subcutaneous white adipose tissue (sWAT) of nondiabetic patients with and without coronary artery disease (CAD). PATIENTS AND METHODS: We evaluated 21 patients with CAD (13 men, age: 68±8 years) and 23 patients without CAD (15 men, age: 66±5 years) who underwent catheterization through the femoral route...
January 12, 2018: Coronary Artery Disease
https://www.readbyqxmd.com/read/29334381/the-molecular-basis-of-subtype-selectivity-of-human-kinin-g-protein-coupled-receptors
#6
Lisa Joedicke, Jiafei Mao, Georg Kuenze, Christoph Reinhart, Tejaswi Kalavacherla, Hendrik R A Jonker, Christian Richter, Harald Schwalbe, Jens Meiler, Julia Preu, Hartmut Michel, Clemens Glaubitz
G-protein-coupled receptors (GPCRs) are the most important signal transducers in higher eukaryotes. Despite considerable progress, the molecular basis of subtype-specific ligand selectivity, especially for peptide receptors, remains unknown. Here, by integrating DNP-enhanced solid-state NMR spectroscopy with advanced molecular modeling and docking, the mechanism of the subtype selectivity of human bradykinin receptors for their peptide agonists has been resolved. The conserved middle segments of the bound peptides show distinct conformations that result in different presentations of their N and C termini toward their receptors...
January 15, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29333632/binding-of-cu-and-cu2-with-peptides-peptides-oxytocin-arg8-vasopressin-bradykinin-angiotensin-i-substance-p-somatostatin-and-neurotensin
#7
Thankan Jayasekharan, Shyam L Gupta, Vikas Dhiman
The intrinsic binding ability of seven natural peptides (oxytocin, arg8 -vasopressin, bradykinin, angiotensin-I, substance-P, somatostatin, and neurotensin) with copper in two different oxidation states (CuI/II ) derived from different Cu+/2+ precursor sources have been investigated for their charge dependent binding characteristics. The peptide-CuI/II complexes, [M - (n-1)H + nCuI ] and [M - (2n-1)H + nCuII ] are prepared/generated by the reaction of peptides with CuI solution/Cu-target and CuSO4 solution, and are analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS)...
January 15, 2018: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29330844/bradykinin-mediates-the-association-of-collecting-duct-cells-to-form-migratory-colonies-through-b2-receptor-activation
#8
Edith Del Valle Guaytima, Yamila Romina Brandán, Nicolás Octavio Favale, Bruno Jaime Santacreu, Norma B Sterin-Speziale, María Gabriela Márquez
It is known that bradykinin (BK) B2 receptor (B2R) is expressed in the collecting duct (CD) cells of the newborn rat kidney, but little is known about its role during early postnatal life. Therefore, we hypothesize that BK could participate in the mechanisms that mediate CD formation during the postnatal renal development. Performing primary cultures, combined with biochemical, immunocytochemical, and time-lapse analysis, we studied the role of BK in CD cell behaviour isolated from renal papilla of neonatal rats...
January 13, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29318628/the-international-wao-eaaci-guideline-for-the-management-of-hereditary-angioedema-the-2017-revision-and-update
#9
Marcus Maurer, Markus Magerl, Ignacio Ansotegui, Emel Aygören Pürsün, Stephen Betschel, Konrad Bork, Tom Bowen, Henrik Balle Boysen, Henriette Farkas, Anete Grumach, Michihiro Hide, Constance Katelaris, Richard Lockey, Hilary Longhurst, William Lumry, Inmaculada Martinez-Saguer, Dumitru Moldovan, Alexander Nast, Ruby Pawankar, Paul Potter, Marc Riedl, Bruce Ritchie, Lanny Rosenwasser, Mario Sánchez-Borges, Yuxiang Zhi, Bruce Zuraw, Timothy Craig
Hereditary angioedema (HAE) is a rare disease and a serious health problem, globally and for affected patients and their families. The pathophysiological background is primarily a vascular reaction to an overshooting local production of bradykinin. Evidence-based recommendations are needed to inform and guide clinical decision makers. This is the first revision and update of the global guideline for the diagnosis and management of HAE[5]. It was developed by the World Allergy Organization (WAO) in collaboration with the European Academy of Allergy and Clinical Immunology (EAACI)...
January 10, 2018: Allergy
https://www.readbyqxmd.com/read/29288468/interactions-between-bradykinin-and-plasmin-in-the-endothelial-ca2-response
#10
Yukako Obata, Kazuhiko Takeuchi, Jiazhang Wei, Akio Hakamata, Keiichi Odagiri, Yoshiki Nakajima, Hiroshi Watanabe
Plasmin is a fibrinolytic factor and a serine protease that activates protease-activated receptors (PARs) to produce endothelium-derived relaxing factors such as nitric oxide and prostacyclin. Nitric oxide and prostacyclin production is regulated, at least in part, by the intracellular Ca2+ concentration in various blood vessel types. Bradykinin and plasmin stimulate vascular endothelial cells and work simultaneously in pathophysiological conditions such as thrombosis and inflammation. Here, we explored the interactions between bradykinin and plasmin in the endothelial Ca2+ response using the fluorescent indicator, Fura-2/AM, in primary cultures of porcine aortic endothelial cells (PAECs)...
December 29, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29288064/corrigendum-to-relationship-of-angiotensin-i-converting-enzyme-ace-and-bradykinin-b2-receptor-bdkrb2-polymorphism-with-diabetic-nephropathy-biochimica-et-biophysica-acta-1863-6-2017-1264-1272
#11
Honghong Zou, Guoqing Wu, Jinlei Lv, Gaosi Xu
No abstract text is available yet for this article.
December 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29277445/biased-g-protein-coupled-receptor-agonism-mediates-neu1-sialidase-and-matrix-metalloproteinase-9-crosstalk-to-induce-transactivation-of-insulin-receptor-signaling
#12
Fiona Haxho, Sabah Haq, Myron R Szewczuk
G protein-coupled receptors (GPCR) can participate in a number of signaling pathways, and this property led to the concept of biased GPCR agonism. Agonists, antagonists and allosteric modulators can bind to GPCRs in different ways, creating unique conformations that differentially modulate signaling through one or more G proteins. A unique neuromedin B (NMBR) GPCR-signaling platform controlling mammalian neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP9) crosstalk has been reported in the activation of the insulin receptor (IR) through the modification of the IR glycosylation...
December 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29260240/a-cyclic-pathway-of-p2%C3%A2-%C3%A3-%C3%A2-7-bradykinin-and-dopamine-receptor-activation-induces-a-sustained-articular-hyperalgesia-in-the-knee-joint-of-rats
#13
Juliana Maia Teixeira, Carlos Amílcar Parada, Cláudia Herrera Tambeli
OBJECTIVE: We investigated whether: (1) P2 × 7 receptor activation by its agonist (BzATP) induces articular hyperalgesia in the rat's knee joint via inflammatory mechanisms and (2) activation of P2 × 7 receptors by endogenous ATP contributes to the articular hyperalgesia induced by bradykinin, TNF-α, IL-1β, CINC-1, PGE2, and dopamine. METHODS: The articular hyperalgesia was quantified using the rat knee joint incapacitation test. The knee joint inflammation, characterized by the concentration of pro-inflammatory cytokines and by neutrophil migration, was quantified in the synovial lavage fluid by ELISA and myeloperoxidase enzyme activity assay, respectively...
December 19, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29250740/blockade-of-bradykinin-receptors-worsens-the-dystrophic-phenotype-of-mdx-mice-differential-effects-for-b1-and-b2-receptors
#14
María José Acuña, Daniela Salas, Adriana Córdova-Casanova, Meilyn Cruz-Soca, Carlos Céspedes, Carlos P Vio, Enrique Brandan
The Kallikrein Kinin System (KKS) is a vasoactive peptide system with known functions in the maintenance of tissue homeostasis, renal function and blood pressure. The main effector peptide of KKS is Bradykinin (BK). This ligand has two receptors: a constitutive B2 receptor (B2R), which has been suggested to have anti-fibrotic effects in renal and cardiac models of fibrosis; and the inducible B1 receptor (B1R), whose expression is induced by damage and inflammation. Inflammation and fibrosis are hallmarks of Duchenne muscular dystrophy (DMD), therefore we hypothesized that the KKS may play a role in this disease...
December 17, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29250329/effect-of-agtr1-and-bdkrb2-gene-polymorphisms-on-atorvastatin-metabolism-in-a-mexican-population
#15
Sarahí Herrera-González, Denisse Aideé Martínez-Treviño, Marcelino Aguirre-Garza, Magdalena Gómez-Silva, Hugo Alberto Barrera-Saldaña, Rafael Baltazar Reyes León-Cachón
Discrepancies in the response to drugs are partially due to polymorphisms in genes involved in drug metabolism and transport. The frequency, pattern and impact of these polymorphisms vary among populations. In the present study, the pharmacokinetics and pharmacogenetics of atorvastatin (ATV) in a Mexican population were investigated. The study cohort exhibited differing ATV metabolizing phenotypes, and in subsequent allelic discrimination assays, single nucleotide polymorphisms in the angiotensinogen, angiotensin II type 1 receptor (AGTR1) and bradykinin B2 receptor (BDKRB2) genes were genotyped and their effects on the pharmacokinetic parameters of ATV were assessed...
December 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29240458/genome-wide-analysis-of-uveal-melanoma-metastasis-associated-lncrnas-and-their-functional-network
#16
Binbin Xu, Ruiqi Ma, Hui Ren, Jiang Qian
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Up to 50% of primary UM cases will develop distant metastasis, but no effective therapies are currently available. The present study aimed to characterize the expression profile of the long noncoding RNAs (lncRNAs) and screen the potential metastasis-associated lncRNAs in UM. A genome-wide analysis of the transcriptome was performed on 11 primary UM tissues (6 metastasized and 5 nonmetastasized) through RNA sequencing. A total of 40,878 lncRNAs were detected in UM, 4,983 of which were novel candidates...
December 14, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/29236387/effect-of-3-substituted-1-4-benzodiazepin-2-ones-on-bradykinin-induced-smooth-muscle-contraction
#17
P A Virych, O V Shelyuk, T A Kabanova, E I Khalimova, V S Martynyuk, V I Pavlovsky, S A Andronati
Biochemical properties of 3-substituted 1,4-benzodiazepine determined by the characteristics of their chemical structure. Influence of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate and amplitudes of isometric smooth muscle contraction in rats was investigated. Compounds MX-1775 and MX-1828 demonstrated the similar inhibition effect on bradykinin-induced contraction of smooth muscle like competitive inhibitor des-arg9-bradykinin-acetate to bradykinin B2-receptors. MX-1626 demonstrated unidirectional changes of maximal normalized rate and force of smooth muscle that proportionally depended on bradykinin concentration in the range 10-10-10-6 M...
January 2017: Ukrainian Biochemical Journal
https://www.readbyqxmd.com/read/29229532/inflammation-and-renal-fibrosis-recent-developments-on-key-signaling-molecules-as-potential-therapeutic-targets
#18
REVIEW
Wenshan Lv, George W Booz, Yangang Wang, Fan Fan, Richard J Roman
Chronic kidney disease (CKD) is a major public health issue. At the histological level, renal fibrosis is the final common pathway of progressive kidney disease irrespective of the initial injury. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Some of the inflammatory signaling molecules involved in CKD include: monocyte chemoattractant protein-1 (MCP-1), bradykinin B1 receptor (B1R), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNFα), transforming growth factor β (TGF-β), and platelet-derived growth factor (PDGF)...
February 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29227570/high-molecular-weight-kininogen-breaking-bad-in-lethal-endotoxemia
#19
Z L M Hofman, S De Maat, C Maas
Kinin formation is a powerful inflammatory process. In the intravascular compartment, bradykinin (RPPGFSPFR) is uniquely released from high-molecular-weight kininogen (HK) after activation of the plasma contact system (reviewed in [1]) and acts on its cognate kinin B2 receptor (B2R), which is constitutively expressed on endothelial cells. The action of carboxypeptidase N (which removes C-terminal arginines) converts bradykinin into des-Arg9 -bradykinin. This article is protected by copyright. All rights reserved...
December 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29226721/investigational-drugs-in-phase-i-and-phase-ii-clinical-trials-for-hereditary-angioedema
#20
Henriette Farkas, Márta Lídia Debreczeni, Kinga Viktória Kőhalmi
Hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) is a rare bradykinin-mediated disease characterized by recurrent subcutaneous and/or submucosal angioedematous attacks (HAE attacks), which occur unpredictably. The recurrent HAE attacks do not respond to conventional treatments, and may evolve into a life-threatening condition; therefore, special therapy is required. Areas covered: The agents used so far for the acute management of HAE attacks act by blocking the release of bradykinin, or its binding to its receptor...
January 2018: Expert Opinion on Investigational Drugs
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