Cyclooxygenase Pathway

Total Page:16

File Type:pdf, Size:1020Kb

Cyclooxygenase Pathway Cyclooxygenase Pathway Diverse physical, chemical, Phospholipase A Glucocorticoids inflammatory, and 2 mitogenic stimuli NSAIDs NSAIDs Arachidonic Acid Prostaglandin G2 CYCLOOXYGENASE Prostaglandin G2 Prostaglandin H Prostaglandin H Synthase-1 Synthase-2 (COX 1) (COX 2) Prostaglandin H2 PEROXIDASE Prostaglandin H2 Tissue Specific Isomerases Prostacyclin Thromboxane A2 Prostaglandin D2 Prostaglandin E2 Prostaglandin F2α IP TPα, TPβ DP1, DP2 EP1, EP2, EP3, EP4 FPα, FPβ Endothelium, Kidney, Platelets, Vascular Mast Cells, Brain, Brain, Kidney, Vascular Uterus, Airways, Vascular Platelets, Brain Smooth Muscle Cells, Airways, Lymphocytes, Smooth Muscle Cells, Smooth Muscle Cells, Macrophages, Kidney Eosinophils Platelets Eyes Prostacyclin Item No. Product Features Prostacyclin (Prostaglandin I2; PGI2) is formed from arachidonic acid primarily in the vascular endothelium and renal cortex by sequential 515211 6-keto • Sample Types: Culture Medium | Plasma Prostaglandin • Measure 6-keto PGF levels down to 6 pg/ml activities of COX and prostacyclin synthase. PGI2 is non-enzymatically 1α F ELISA Kit • Incubation : 18 hours | Development: 90-120 minutes | hydrated to 6-keto PGF1α (t½ = 2-3 minutes), and then quickly converted 1α Read: Colorimetric at 405-420 nm to the major metabolite, 2,3-dinor-6-keto PGF1α (t½= 30 minutes). Prostacyclin was once thought to be a circulating hormone that regulated • Assay 24 samples in triplicate or 36 samples in duplicate platelet-vasculature interactions, but the rate of secretion into circulation • NOTE: A portion of urinary 6-keto PGF1α is of renal origin coupled with the short half-life indicate that prostacyclin functions • NOTE : It has been found that normal plasma levels of 6-keto PGF may be low locally. Estimates of systemic PGI2 production have often been assessed 1α by measurement of 6-keto PGF1α alone or in combination with 2,3-dinor- 501100 Prostaglandin I • Sample Type: Urine 6-keto PGF1α. However, the majority of 6-keto PGF1α in urine is of renal Metabolite • Measure PGIM down to 120 pg/ml origin with only 14% originating from plasma. ELISA Kit • Convenient overnight format COOH • NOTE : A minimum of a 1:10 dilution is recommended Arachidonic Acid when assaying urine samples Sample types not noted may still be assayed but have not been validated by Cayman Scientists COX O COOH PGH Prostacyclin Pathway Reagents 2 O Synthase OH Antibodies/Probes Agonists Antagonists Inhibitor Prostacyclin Synthase IP Receptor (human) Prostaglandin I2 CAY10441 U-51605 Polyclonal Antibody (sodium salt) 10005186 16465 10005518 18220 COO- Na+ AFP 07 (free acid) O IP Receptor (mouse) CAY10449 Polyclonal Antibody 13626 10005913 PGI2 160070 Beraprost (sodium salt) HO 18230 OH Prostaglandin I Synthase Polyclonal Antibody Iloprost Non-enzymatic 160640 18215 OH NS-304 COOH Prostaglandin I Synthase 6-keto PGF1α 10010411 O Monoclonal HO Antibody (Clone isn-1) Carbaprostacyclin OH 160630 18210 -oxidation Cicaprost β Prostaglandin I Synthase 16831 OH Monoclonal Antibody COO- Na+ Ciprostene (calcium salt) 2,3-dinor-6-keto PGF1α (Clone 3C8) O 10247 18216 HO Treprostinil OH Prostaglandin I Synthase 10162 (mouse) Polyclonal Antibody MRE-269 100023 10010412 Taprostene (free acid) Anti-PGI 10011348 Synthase:SureLight® R-PE 16690 Thromboxane A2 O COOH O Thromboxane A (TXA ) is produced from arachidonic acid by many cells and 2 2 PGH OH causes irreversible platelet aggregation and vascular and bronchial smooth 2 Thromboxane Synthase muscle contraction. TXA2, like most lipid mediators, is not a circulating hormone. It is formed in response to local stimuli and exerts its effects within a short distance of its biosynthesis. TXA is rapidly hydrolyzed non-enzymatically COOH 2 O to form thromboxane B2 (TXB2). Although it is common to estimate TXA2 levels TXA OH by measuring TXB2, most of the TXB2 measured is due to ex vivo platelet 2 activation or intra-renal production. Measurement errors are compounded Non-enzymatic by the fact that normal concentrations of circulating TXB are extremely low 2 OH (1-2 pg/ml), and highly transient (t = 5-7 minutes). To circumvent this problem, ½ COOH it is necessary to measure a metabolite that cannot be formed by platelets or HO O by the kidney. TXB2 may be metabolized by 11-hydroxy TX dehydrogenase OH TXB2 to form 11-dehydro TXB2, or by β-oxidation to form 2,3-dinor TXB2. Infusion 11-hydroxy TX dehydrogenase β-oxidation studies using TXB2 have shown that both metabolites are formed equally, although 11-dehydro TXB2 has a longer circulating half-life (t½ = 45 minutes). OH Therefore, measurement of 11-dehydro TXB2 in plasma or urine will give a OH COOH COOH time-integrated indication of TXA2 production. The circulating half-life of O 2,3-dinor TXB2 is shorter (t = 15 minutes). Therefore, measurement of O HO O ½ OH 2,3-dinor TXB will give a more episodic indication of TXA production. OH 2 2 11-dehydro TXB2 2,3-dinor TXB2 2 Cayman Chemical • Ann Arbor, MI 48108 • 800.364.9897 • www.caymanchem.com Thromboxane Pathway Reagents Antibodies/Probes Agonists Antagonists Synthase Inhibitors TP Receptor (human) Polyclonal FITC Antibody 10012559 Carbocyclic Thromboxane A2 19010 I-SAP 19021 Furegrelate (sodium salt) 70540 TP Receptor (human) Polyclonal Antibody 10004452 U-46619 16450 BAY-u3405 10156 Ozagrel 70515 TP Receptor (mouse) Polyclonal Antibody 101882 I-BOP 19600 SQ 29,548 19025 1-Benzylimidazole 70510 Thromboxane B2 11-dehydrogenase Polyclonal Antiserum 160720 U-44069 16440 Seratrodast 9002014 BM 567 10155 Thromboxane Synthase Polyclonal Antibody 160715 S18886 14059 GW 627368X 10009162 BM 567 10155 CAY10535 10010396 AH 23848 (calcium salt) 19023 L-655,240 10011562 Thromboxane B2 A portion of TXB2 measured in urine is of renal origin and does not represent systemic TXB2 formation, thus selecting an appropriate assay for urinary TXB2 is dependent on the application. The TX metabolite 11-dehydro TXB2 is better suited for measurement of systemically produced TXB2 in urine samples. Item No. Product Features 501020 Thromboxane B2 ELISA Kit • Sample Types: Culture Medium | Serum | Urine • Measure TXB2 levels down to 5 pg/ml • Incubation : 18 hours | Development: 90-120 minutes | Read: Colorimetric at 405-420 nm • Assay 24 samples in triplicate or 36 samples in duplicate 10004023 Thromboxane B2 Express ELISA Kit - Monoclonal • Sample Types: Culture Medium | Serum | Plasma • Measure TXB2 levels down to 45 pg/ml • Rapid assay; get results in under 4 hours • Assay 24 samples in triplicate or 36 samples in duplicate 519510 11-dehydro Thromboxane B2 ELISA Kit - Monoclonal • Sample Type: Urine • Assay 24 samples in triplicate or 36 samples in duplicate • Incubation: 18 hours | Development: 60-90 minutes | Read: Colorimetric at 405-420 nm • Assay 24 samples in triplicate or 36 samples in duplicate • Detect 11-dehydro TXB2, a stable urinary metabolite of TXA2 and TXB2 Sample types not noted may still be assayed but have not been validated by Cayman Scientists Prostaglandin D2 Prostaglandin D2 (PGD2) is biosynthesized in the brain by a soluble, 26 kDa glutathione- O COOH O independent lipocalin-type PGD2 synthase. This PGD2 accumulates in the cerebrospinal PGH2 OH fluid (CSF), where it induces physiologic sleep in rats and humans. PGD2 is also PGD Synthase synthesized in mast cells and leukocytes by a cellular, myeloid-type, glutathione- OH dependent PGD synthase. This PGD2, which is formed in intracellular and vascular COOH compartments, is rapidly metabolized to O OH 11β-PGF2α. Thus, urinary measurements PGD2 of PGD2 synthesis are most appropriately focused on the measurement of 11β-PGF2α. Measurement of the parent eicosanoid PGD2 is appropriate in the supernatants OH of cell cultures, where PGD2 levels may reach several ng/ml, and in CSF, where COOH concentrations of several hundred pg/ml HO have been measured. OH 11β-PGF2α For full information on these products and more, visit www.caymanchem.com 3 Item No. Product Features 512031 Prostaglandin D2 ELISA Kit • Sample Types: Cell Lysates | Culture Medium • Measure PGD2 levels down to 55 pg/ml • Incubation: 18 hours | Development: 90-120 minutes | Read: Colorimetric at 405-420 nm • Assay 24 samples in triplicate or 36 samples in duplicate 512041 Prostaglandin D2 Express ELISA Kit • Sample Types: Cell Lysates | Culture Medium • Measure PGD2 levels down to 350 pg/ml • Rapid assay; get results in under 4 hours • Assay 24 samples in triplicate or 36 samples in duplicate 512011 Prostaglandin D2-MOX ELISA Kit • Sample Types: Culture Medium | Plasma • Measure PGD2-MOX levels down to 3.1 pg/ml • Incubation: 18 hours | Development: 90-120 minutes | Read: Colorimetric at 405-420 nm • Treatment of samples with MOX hydrochloride converts unstable PGD2 to stable PGD2-MOX • Highly sensitive • NOTE: Derivatization of standards and samples is required before running assay 500151 Prostaglandin D2-MOX Express ELISA Kit • Sample Types: Culture Medium | Plasma • Measure PGD2-MOX levels down to 16 pg/ml • Rapid assay; get results in under 4 hours • Assay 24 samples in triplicate or 36 samples in duplicate • Treatment of samples with MOX hydrochloride converts unstable PGD2 to stable PGD2-MOX; MOX derivatization reagent included with assay 516521 11β-Prostaglandin F2α ELISA Kit • Sample Types: Plasma | Urine • Measure 11β-PGF2α levels down to 5 pg/ml • Incubation: 18 hours | Development: 60-90 minutes | Read: Colorimetric at 405-420 nm • Assay 24 samples in triplicate or 36 samples in duplicate • NOTE: 11β-PGF2α may not be present in mouse urine – see Item No. 501001 501001 tetranor-PGDM
Recommended publications
  • The Aryl Hydrocarbon Receptor: Structural Analysis and Activation Mechanisms
    The Aryl Hydrocarbon Receptor: Structural Analysis and Activation Mechanisms This thesis is submitted in fulfilment of the requirements for the degree of Doctor of Philosophy in the School of Molecular and Biomedical Sciences (Biochemistry), The University of Adelaide, Australia Fiona Whelan, B.Sc. (Hons) 2009 2 Table of Contents THESIS SUMMARY................................................................................. 6 DECLARATION....................................................................................... 7 PUBLICATIONS ARISING FROM THIS THESIS.................................... 8 ACKNOWLEDGEMENTS...................................................................... 10 ABBREVIATIONS ................................................................................. 12 CHAPTER 1: INTRODUCTION ............................................................. 17 1.1 BHLH.PAS PROTEINS ............................................................................................17 1.1.1 General background..................................................................................17 1.1.2 bHLH.PAS Class I Proteins.........................................................................18 1.2 THE ARYL HYDROCARBON RECEPTOR......................................................................19 1.2.1 Domain Structure and Ligand Activation ..............................................19 1.2.2 AhR Expression and Developmental Activity .......................................21 1.2.3 Mouse AhR Knockout Phenotype ...........................................................23
    [Show full text]
  • AA Metabolism, 139 A2b1, 69, 70, 318–323 ABCB1 Gene, 176 Abciximab
    Index A aIIbb3, 60, 62, 69, 70, 73, 74, 79, 80 AA. See Arachidonic acid (AA) AJW202, 293 AA metabolism, 139 Akt-1, 345 a2b1, 69, 70, 318–323 Akt-2, 345 ABCB1 gene, 176 ALX-0081, 296 Abciximab, 206–208, 497, 500, 501, 504–505, ALX-0681, 298 509, 513, 514, 525 Anagrelide, 227, 229 approval, 206 Ankle brachial indexes (ABIs), 549, 587, EPIC trial, 207 595–597 EPILOG study, 207 framingham risk score, 551 EPISTENT study, 207 screening, 550 platelet binding, 207 sensitivity, 551 thrombocytopenia, 206 specificity, 551 in unstable angina, 208 vascular risk, 550 ABIs. See Ankle brachial indexes (ABIs) Antagomirs, 439 Acetylsalicylic acid (aspirin), 137–158 Antibodies, 317 ACS. See Acute coronary syndromes (ACS) Anticoagulants, 525, 537 Acute coronary syndromes (ACS), 288 Anticoagulation, 533, 534 Acute ischemic stroke, 143, 149–150 Antioxidant, 233 Acute myocardial infarction, 142, 143, 149, Antiplatelet agents, 263, 553 153, 157 Antithrombotic Trialist’s ADAMTS-13, 93 Collaboration, 553 Adenosine diphosphate (ADP), 37, 88, 96, aspirin, 553 166, 473 clopidogrel, 553 Adenosine triphosphate (ATP), 37 dipyridamole, 553 Adhesion, 90, 112–118, 125 meta-analysis, 560 Adhesion molecules infiltration, 264 picotamide, 553 Adiponectin, 315 risk reduction, 553 ADP. See Adenosine diphosphate (ADP) ticlopidine, 553 ADP inhibitors (or P2Y12 blockers), 497–499, vascular events, 553 501–505, 507–509, 513, 514 Antiplatelet therapy, 472 ADP-receptor antagonists, 169 Apixaban, 535, 539 Adverse effects, 153–156 Aptamers, 299–301 Aegyptin, 327 Arachidonic acid (AA), 474 P. Gresele et al. (eds.), Antiplatelet Agents, Handbook of Experimental 607 Pharmacology 210, DOI 10.1007/978-3-642-29423-5, # Springer-Verlag Berlin Heidelberg 2012 608 Index ARC1779, 299–300 TXS signaling, 279 ARC15105, 300 Cardiovascular death, 248 AR-C69931MX, 456 Carotid endarterectomy (ACE) inhibition, Aspirin, 474, 496, 498–499, 501–502, 143, 156 504–507, 511–514, 520, 522, Carotid stenosis, 523 527, 531, 533–537, 539, CCBs.
    [Show full text]
  • Open Thesis Master Document V5.0.Pdf
    The Pennsylvania State University The Graduate School Department of Veterinary and Biomedical Science IDENTIFICATION OF ENDOGENOUS MODULATORS FOR THE ARYL HYDROCARBON RECEPTOR A Thesis in Genetics by Christopher R. Chiaro © 2007 Christopher R. Chiaro Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December, 2007 The thesis of Christopher R. Chiaro was reviewed and approved* by the following: Gary H. Perdew John T. and Paige S. Smith Professor in Agricultural Sciences Thesis Advisor Chair of Committee C. Channa Reddy Distinguished Professor of Veterinary Science A. Daniel Jones Senior Scientist Department of Chemistry John P. Vanden Heuvel Professor of Veterinary Science Richard Ordway Associate Professor of Biology Chair of Genetics Graduate Program *Signatures are on file in the Graduate School iii ABSTRACT The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor capable of being regulated by a structurally diverse array of chemicals ranging from environmental carcinogens to dietary metabolites. A member of the basic helix-loop- helix/ Per-Arnt-Sim (bHLH-PAS) super-family of DNA binding regulatory proteins, the AhR is an important developmental regulator that can be detected in nearly all mammalian tissues. Prior to ligand activation, the AhR resides in the cytosol as part of an inactive oligomeric protein complex comprised of the AhR ligand-binding subunit, a dimer of the 90 kDa heat shock protein, and a single molecule each of the immunophilin like X-associated protein 2 (XAP2) and p23 proteins. Functioning as chemosensor, the AhR responds to both endobiotic and xenobiotic derived chemical ligands by ultimately directing the expression of metabolically important target genes.
    [Show full text]
  • Epigenetic Regulations of Ahr in the Aspect of Immunomodulation
    International Journal of Molecular Sciences Review Epigenetic Regulations of AhR in the Aspect of Immunomodulation Anna Wajda 1,* , Joanna Łapczuk-Roma ´nska 2 and Agnieszka Paradowska-Gorycka 1 1 Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland; [email protected] 2 Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] * Correspondence: [email protected] Received: 31 July 2020; Accepted: 28 August 2020; Published: 3 September 2020 Abstract: Environmental factors contribute to autoimmune disease manifestation, and as regarded today, AhR has become an important factor in studies of immunomodulation. Besides immunological aspects, AhR also plays a role in pharmacological, toxicological and many other physiological processes such as adaptive metabolism. In recent years, epigenetic mechanisms have provided new insight into gene regulation and reveal a new contribution to autoimmune disease pathogenesis. DNA methylation, histone modifications, chromatin alterations, microRNA and consequently non-genetic changes in phenotypes connect with environmental factors. Increasing data reveals AhR cross-roads with the most significant in immunology pathways. Although study on epigenetic modulations in autoimmune diseases is still not well understood, therefore future research will help us understand their pathophysiology and help to find new therapeutic strategies. Present literature review
    [Show full text]
  • Prostaglandin D2 and the Role of the DP1, DP2 and TP Receptors in the Control of Airway Reflex Events
    ERJ Express. Published on October 16, 2014 as doi: 10.1183/09031936.00061614 ORIGINAL ARTICLE IN PRESS | CORRECTED PROOF Prostaglandin D2 and the role of the DP1, DP2 and TP receptors in the control of airway reflex events Sarah A. Maher1, Mark A. Birrell1,2, John J. Adcock1, Michael A. Wortley1, Eric D. Dubuis1, Sara J. Bonvini1, Megan S. Grace1 and Maria G. Belvisi1,2 Affiliations: 1Respiratory Pharmacology, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK. 2MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK. Correspondence: Maria G. Belvisi, Imperial College London, Respiratory Pharmacology, NHLI, Sir Alexander Fleming Building, Exhibition Road, London, SW7 2AZ, UK. E-mail: [email protected] ABSTRACT Prostaglandin D2 (PGD2) causes cough and levels are increased in asthma suggesting that it may contribute to symptoms. Although the prostaglandin D2 receptor 2 (DP2) is a target for numerous drug discovery programmes little is known about the actions of PGD2 on sensory nerves and cough. We used human and guinea pig bioassays, in vivo electrophysiology and a guinea pig conscious cough model to assess the effect of prostaglandin D2 receptor (DP1), DP2 and thromboxane receptor antagonism on PGD2 responses. PGD2 caused cough in a conscious guinea pig model and an increase in calcium in airway jugular ganglia. Using pharmacology and receptor-deficient mice we showed that the DP1 receptor mediates sensory nerve activation in mouse, guinea pig and human vagal afferents. In vivo, PGD2 and a DP1 receptor agonist, but not a DP2 receptor agonist, activated single airway C-fibres.
    [Show full text]
  • Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome
    International Journal of Molecular Sciences Review Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome Stefano Turolo 1,* , Alberto Edefonti 1 , Alessandra Mazzocchi 2, Marie Louise Syren 2, William Morello 1, Carlo Agostoni 2,3 and Giovanni Montini 1,2 1 Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Pediatric Nephrology, Dialysis and Transplant Unit, Via della Commenda 9, 20122 Milan, Italy; [email protected] (A.E.); [email protected] (W.M.); [email protected] (G.M.) 2 Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy; [email protected] (A.M.); [email protected] (M.L.S.); [email protected] (C.A.) 3 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pediatric Intermediate Care Unit, 20122 Milan, Italy * Correspondence: [email protected] Abstract: Studies concerning the role of arachidonic acid (AA) and its metabolites in kidney disease are scarce, and this applies in particular to idiopathic nephrotic syndrome (INS). INS is one of the most frequent glomerular diseases in childhood; it is characterized by T-lymphocyte dysfunction, alterations of pro- and anti-coagulant factor levels, and increased platelet count and aggregation, leading to thrombophilia. AA and its metabolites are involved in several biological processes. Herein, Citation: Turolo, S.; Edefonti, A.; we describe the main fields where they may play a significant role, particularly as it pertains to their Mazzocchi, A.; Syren, M.L.; effects on the kidney and the mechanisms underlying INS. AA and its metabolites influence cell Morello, W.; Agostoni, C.; Montini, G.
    [Show full text]
  • 4 Supplementary File
    Supplemental Material for High-throughput screening discovers anti-fibrotic properties of Haloperidol by hindering myofibroblast activation Michael Rehman1, Simone Vodret1, Luca Braga2, Corrado Guarnaccia3, Fulvio Celsi4, Giulia Rossetti5, Valentina Martinelli2, Tiziana Battini1, Carlin Long2, Kristina Vukusic1, Tea Kocijan1, Chiara Collesi2,6, Nadja Ring1, Natasa Skoko3, Mauro Giacca2,6, Giannino Del Sal7,8, Marco Confalonieri6, Marcello Raspa9, Alessandro Marcello10, Michael P. Myers11, Sergio Crovella3, Paolo Carloni5, Serena Zacchigna1,6 1Cardiovascular Biology, 2Molecular Medicine, 3Biotechnology Development, 10Molecular Virology, and 11Protein Networks Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 34149, Trieste, Italy 4Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy 5Computational Biomedicine Section, Institute of Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany 6Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy 7National Laboratory CIB, Area Science Park Padriciano, Trieste, 34149, Italy 8Department of Life Sciences, University of Trieste, Trieste, 34127, Italy 9Consiglio Nazionale delle Ricerche (IBCN), CNR-Campus International Development (EMMA- INFRAFRONTIER-IMPC), Rome, Italy This PDF file includes: Supplementary Methods Supplementary References Supplementary Figures with legends 1 – 18 Supplementary Tables with legends 1 – 5 Supplementary Movie legends 1, 2 Supplementary Methods Cell culture Primary murine fibroblasts were isolated from skin, lung, kidney and hearts of adult CD1, C57BL/6 or aSMA-RFP/COLL-EGFP mice (1) by mechanical and enzymatic tissue digestion. Briefly, tissue was chopped in small chunks that were digested using a mixture of enzymes (Miltenyi Biotec, 130- 098-305) for 1 hour at 37°C with mechanical dissociation followed by filtration through a 70 µm cell strainer and centrifugation.
    [Show full text]
  • Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr
    Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine
    [Show full text]
  • Vasoactive Responses of U46619, PGF2 , Latanoprost, and Travoprost
    Vasoactive Responses of U46619, PGF2␣, Latanoprost, and Travoprost in Isolated Porcine Ciliary Arteries Ineta Vysniauskiene, Reto Allemann, Josef Flammer, and Ivan O. Haefliger PURPOSE. To compare the vasoactive properties of the prosta- these responses can be modulated by SQ 29548 (TP-receptor noids U46619 (thromboxane A2 analogue), prostaglandin F2␣ antagonist) or AL-8810 (FP-receptor antagonist). (PGF2␣), latanoprost free acid, and travoprost free acid in isolated porcine ciliary arteries. METHODS. In a myograph system (isometric force measure- MATERIAL AND METHODS ment), quiescent vessels were exposed (cumulatively) to U46619, PGF , latanoprost, or travoprost (0.1 nM–0.1 mM). 2␣ Vessels Preparation Experiments were also conducted in the presence of SQ 29548 (TP-receptor antagonist; 3–10 ␮M) or AL-8810 (FP-receptor Porcine eyes were obtained from an abattoir immediately after death. antagonist; 3–30 ␮M). Contractions were expressed as the In cold modified Krebs-Ringer solution (NaCl 118 mM, KCl 4.7 mM, percentage of 100 mM potassium chloride-induced contrac- CaCl2 2.5 mM, K2PO4 1.2 mM, MgSO4 1.2 mM, NaHCO3 25 mM, tions. glucose 11.1 mM, and EDTA 0.026 mM), ciliary arteries were dissected 5 ␮ RESULTS. In quiescent vessels, contractions (concentration–re- and cut into 2-mm segments. In an organ chamber, two 45- m Ϯ tungsten wires were passed through the vessel’s lumen and attached to sponse curves) induced by (0.1 mM) PGF2␣ (87.9% 3.5%), U46619 (66.7% Ϯ 4.1%), and latanoprost (62.9% Ϯ 3.6%) were a force transducer for isometric force measurements (Myo-Interface; JP more pronounced (P Յ 0.001) than those induced by tra- Trading, Aarhus, Denmark).
    [Show full text]
  • Effect of Prostanoids on Human Platelet Function: an Overview
    International Journal of Molecular Sciences Review Effect of Prostanoids on Human Platelet Function: An Overview Steffen Braune, Jan-Heiner Küpper and Friedrich Jung * Institute of Biotechnology, Molecular Cell Biology, Brandenburg University of Technology, 01968 Senftenberg, Germany; steff[email protected] (S.B.); [email protected] (J.-H.K.) * Correspondence: [email protected] Received: 23 October 2020; Accepted: 23 November 2020; Published: 27 November 2020 Abstract: Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. In this review, we focus on their influence on platelets, which are key elements in thrombosis and hemostasis. The function of platelets is influenced by mediators in the blood and the vascular wall. Activated platelets aggregate and release bioactive substances, thereby activating further neighbored platelets, which finally can lead to the formation of thrombi. Prostanoids regulate the function of blood platelets by both activating or inhibiting and so are involved in hemostasis. Each prostanoid has a unique activity profile and, thus, a specific profile of action. This article reviews the effects of the following prostanoids: prostaglandin-D2 (PGD2), prostaglandin-E1, -E2 and E3 (PGE1, PGE2, PGE3), prostaglandin F2α (PGF2α), prostacyclin (PGI2) and thromboxane-A2 (TXA2) on platelet activation and aggregation via their respective receptors. Keywords: prostacyclin; thromboxane; prostaglandin; platelets 1. Introduction Hemostasis is a complex process that requires the interplay of multiple physiological pathways. Cellular and molecular mechanisms interact to stop bleedings of injured blood vessels or to seal denuded sub-endothelium with localized clot formation (Figure1).
    [Show full text]
  • Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive Rats
    J Pharmacol Sci 91, 305 – 312 (2003) Journal of Pharmacological Sciences ©2003 The Japanese Pharmacological Society Full Paper Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive Rats Yasuko Karasawa1, Hiroko Komiyama1, Shigeru Yoshida1, Noriko Hino1, Yasuhiro Katsuura2, Shiro Nakaike1 and Hiroaki Araki3,* 1Pharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd., Yoshino-cho 1-403, Saitama 330-8530, Japan 2Pharmacological Research Department, Teijin Ltd., 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan 3Department of Hospital Pharmacy, Ehime University School of Medicine, Shiktsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan Received November 14, 2002; Accepted January 30, 2003 Abstract. We investigated the effect of TTC-909, a drug preparation of the stable prostaglandin I2 analogue clinprost (isocarbacyclin methylester; methyl 5-{(1S,5S,6R,7R)-7- hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl] bicyclo[3.3.0]oct-2-en-3-yl} pentanoate) incorporated into lipid microspheres, on cerebral infarction 7 days after permanent occlusion of the middle cerebral artery (MCA) in stroke prone spontaneously hypertensive rats (SHRSP). Under the anesthesia, the MCA was permanently occluded above the rhinal fissure. In schedule 1, vehicle or TTC-909 was injected i.v. once daily over 7 days starting immediately after MCA occlusion. In schedule 2, vehicle or TTC-909 was infused for 3 h starting immediately after MCA occlusion. In schedule 3, vehicle or TTC-909 was infused for 3 h starting immediately after MCA occlusion followed by bolus injection once daily over 6 days. Seven days later, the infarct volume was estimated following hematoxylin and eosin staining.
    [Show full text]
  • Japanese Guidelines for Adult Asthma 2020*
    Allergology International xxx (xxxx) xxx Contents lists available at ScienceDirect Allergology International journal homepage: http://www.elsevier.com/locate/alit Invited Review Article Japanese guidelines for adult asthma 2020* * Yoichi Nakamura a, , Jun Tamaoki b, Hiroyuki Nagase c, Masao Yamaguchi d, Takahiko Horiguchi e, Soichiro Hozawa f, Masakazu Ichinose g, Takashi Iwanaga h, Rieko Kondo e, Makoto Nagata i, Akihito Yokoyama j, Yuji Tohda h, The Japanese Society of Allergology a Medical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross Hospital, Yokohama, Japan b First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan c Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan d Third Department of Medicine, Teikyo University Chiba Medical Center, Chiba, Japan e Department of Respiratory Medicine, Fujita Health University Bantane Hospital, Nagoya, Japan f Hiroshima Allergy and Respiratory Clinic, Hiroshima, Japan g Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan h Department of Respiratory Medicine and Allergology, Kinki University Faculty of Medicine, Osaka, Japan i Department of Respiratory Medicine, Saitama Medical University Hospital, Saitama, Japan j Department of Hematology and Respiratory Medicine, Kochi University, Kochi, Japan article info abstract Article history: Bronchial asthma is characterized by chronic airway inflammation, which manifests clinically as variable Received 9 June 2020 airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma may induce airway Available online xxx remodeling and become intractable. The prevalence of asthma has increased; however, the number of patients who die from it has decreased (1.3 per 100,000 patients in 2018).
    [Show full text]