- PARP1 gene knock-out increases resistance to retinal degeneration without affecting retinal function
Division of Experimental Ophthalmology, Institute for Ophthalmic Research, University of Tubingen, Tubingen, Germany
PLoS ONE 5:e15495. 2010
..Moreover, our results suggest that PARP dependent cell death or PARthanatos may play a major role in retinal degeneration and highlight the possibility to use specific PARP inhibitors for the treatment of RP...
- Excessive activation of cyclic nucleotide-gated channels contributes to neuronal degeneration of photoreceptors
Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, INSERM U 592, Universite Pierre et Marie Curie, Bâtiment Kourilsky 6ème étage, 75571 Paris Cedex 12, France
Eur J Neurosci 22:1013-22. 2005
- The effect of Sildenafil on human platelet secretory function is controlled by a complex interplay between phosphodiesterases 2, 3 and 5
Torsten R Dunkern
Department of Biochemistry Inflammation, ALTANA Pharma AG, Byk Gulden Str 2, Konstanz 78467, Germany
Cell Signal 17:331-9. 2005
- Inhibition of cyclic GMP hydrolysis with zaprinast reduces basal and cyclic AMP-elevated L-type calcium current in guinea-pig ventricular myocytes
Mark T Ziolo
Department of Physiology, Midwestern University, 555 31st Street, Downers Grove, Illinois, IL 60515 USA
Br J Pharmacol 138:986-94. 2003
..This regulation may also be important in disease states in which cGMP production is increased and PDE5 expression is altered, such as heart failure...
- HIV-1 coat protein gp120 decreases NO-dependent cyclic GMP accumulation in rat brain astroglia by increasing cyclic GMP phosphodiesterase activity
Instituto de Biotecnología y Biomedicina V Villar Palasí and Departamento de Bioquímica y Biología Molecular, Universidad Autonoma de Barcelona, 08193 Bellaterra, Spain
Neurochem Int 45:937-46. 2004
..Experiments in whole cells using specific phosphodiesterase inhibitors indicate that the viral protein increases the activity of cGMP specific phosphodiesterase 5...
- Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model
Department of Analytical Chemistry, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe 651-2180 Japan
Br J Pharmacol 133:841-8. 2001
..These findings suggest that ibudilast prevents the H(2)O(2)-induced delayed apoptosis of astrocytes via a cyclic GMP, but not cyclic AMP, signalling pathway...
- Effects of various selective phosphodiesterase inhibitors on carbachol-induced contraction and cyclic nucleotide contents in guinea pig taenia coli
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Musashino, Tokyo, Japan
J Vet Med Sci 66:1047-52. 2004
..In conclusion, it was indicated that vinpocetine- or Ro20-1724-induced relaxation was correlated with cAMP but EHNA- or zaprinast- induced relaxation was correlated with cGMP...
- Cyclic nucleotides and neuroblastoma differentiation
Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy
Nucleosides Nucleotides Nucleic Acids 23:1551-4. 2004
..No appreciable effect was observed using Dipyridamole, another specific PDE5 inhibitor...
- N-acetyl-L-cysteine exerts direct anti-aggregating effect on human platelets
S. Luigi Gonzaga Hospital, Orbassano (TO, Italy
Eur J Clin Invest 31:452-61. 2001
..CONCLUSION: N-acetyl-L-cysteine exerts direct anti-aggregating effects through an increased bioavailability of platelet nitric oxide...
- NSAIDs increase GM-CSF release by human synoviocytes: comparison with nitric oxide-donating derivatives
Cardiac, Vascular and Inflammation Research, The William Harvey Research Institute, Bart s and The London, Queen Mary School of Medicine and Dentistry, London, UK
Eur J Pharmacol 508:7-13. 2005
..NO-ASA is the exception, because it does not increase GM-CSF release, although at millimolar concentrations cell viability is reduced...
- Cyclic GMP-specific phosphodiesterase 5 regulates growth and apoptosis in pulmonary endothelial cells
Dept of Pharmacology, Center for Lung Biology, Univ of So Alabama College of Medicine, CSAB 345, 301 N Univ Blvd, Mobile, AL 36688, USA
Am J Physiol Lung Cell Mol Physiol 289:L196-206. 2005
..Collectively, these data suggest that PDE5-regulated [cGMP]i controls endothelial cell growth and apoptosis, representing a mechanism of heterogeneity between two endothelial phenotypes...
- Increased cGMP phosphodiesterase activity mediates renal resistance to ANP in rats with bile duct ligation
X P Ni
Division of Nephrology, San Francisco General Hospital, and Metabolic Research Unit, University of California San Francisco, San Francisco, California 94143, USA
Kidney Int 59:1264-73. 2001
..Other PDEs could contribute only a minor part to the enhanced cGMP hydrolysis observed in kidneys of CBDL rats. This PDE5-dependent ANP resistance may represent an important contributor to the sodium retention of liver disease...
- Lack of the nitric oxide-cyclic GMP-potassium channel pathway for the antinociceptive effect of intrathecal zaprinast in a rat formalin test
Myung Ha Yoon
Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 8 Hakdong, Dongku, Gwangju 501 757, Republic of Korea
Neurosci Lett 390:114-7. 2005
..However, the NO-sensitive cGMP-potassium channel pathway is not contributable to the antinociceptive mechanism of zaprinast in the spinal cord...
- Postnatal maturation of phosphodiesterase 5 (PDE5) in piglet pulmonary arteries: activity, expression, effects of PDE5 inhibitors, and role of the nitric oxide/cyclic GMP pathway
Department of Pharmacology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
Pediatr Res 56:563-70. 2004
..However, PDE5 is not responsible for the maturational increase of NO bioactivity during the first days of extrauterine life...
- Cyclic nucleotide-dependent phosphodiesterases (PDEI) inhibition by muscarinic antagonists in bovine tracheal smooth muscle
Lérida Guerra de González
Sección de Biomembranas y Cátedra de Patología General y Fisiopatología, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
Biochem Pharmacol 68:651-8. 2004
- The kappa-opioid agonist (+/-)-bremazocine elicits peripheral antinociception by activation of the L-arginine/nitric oxide/cyclic GMP pathway
Luiz H Amarante
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, 6627, Campus da Pampulha, Belo Horizonte, MG 31270 100, Brazil
Eur J Pharmacol 454:19-23. 2002
..Our data suggest that bremazocine elicits peripheral antinociception by activation of the L-arginine/NO/cyclic GMP pathway and that nitric oxide is an intermediary in this mechanism, forming cyclic GMP...
- Incubation of porcine iris-ciliary bodies to study the mechanisms by which nitric oxide donors lower intraocular pressure
Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, University of Helsinki, Finland
Med Sci Monit 9:BR1-7. 2003
..We previously reported that several nitric oxide (NO) donors, guanylate cyclase activators, and cyclic GMP lower intraocular pressure (IOP) in rabbits...
- Effects of rolipram, pimobendan and zaprinast on ischaemia-induced dysrhythmias and on ventricular cyclic nucleotide content in the anaesthetized rat
M D Carceles
University School of Medicine, Department of Anaesthesiology, CSV Arrixaca Hospital, Murcia, Spain
Eur J Anaesthesiol 20:205-11. 2003
..The drugs used were pimobendan, a selective PDE III inhibitor, rolipram, a selective PDE IV inhibitor, and zaprinast, a selective PDE V inhibitor...
- Role of cyclic GMP in nitrous-oxide-induced anxiolytic-like behavior in the mouse light-dark exploration test
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164 6534, USA
Behav Neurosci 118:648-52. 2004
..These preliminary findings suggest that a signaling pathway involving NO and cGMP may mediate the behavioral effects of N2O...
- Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential tissue distribution and subcellular localization of PDE9A variants
Allergy Department, Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 1600, Kenilworth, NJ 07033, USA
Gene 314:15-27. 2003
..We speculate that the physiological role of the PDE9A diversity may be imparting cGMP-metabolizing ability to specific cellular compartments in appropriate tissues...
- Phosphodiesterase inhibitors for persistent pulmonary hypertension of the newborn: a review
J N Travadi
Department of Neonatal Paediatrics, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia
Pediatr Pulmonol 36:529-35. 2003
..The need for randomized-controlled trials to determine the safety, efficacy, and long-term outcome following treatment with sildenafil in PPHN is emphasized...
- Phosphodiesterase-5 inhibition synergizes rho-kinase antagonism and enhances erectile response in male hypertensive rats
Division of Urology, University of California San Diego Medical Center, 200 W Arbor Drive 8897, San Diego, CA 92103 8897, USA
Int J Impot Res 16:187-94. 2004
..Rho-kinase inhibition alone or combined with PDE5 inhibition may be of value in treating hypertension-related ED...
- mAChRs in the grasshopper brain mediate excitation by activation of the AC/PKA and the PLC second-messenger pathways
Department of Neurobiology, Institute of Zoology and Anthropology, Georg August University, Berliner Strasse 28, 37073 Goettingen, Germany
J Neurophysiol 87:876-88. 2002
- Elevation of intracellular cAMP evokes activity-dependent release of adenosine in cultured rat forebrain neurons
Department of Neurology and Program in Neuroscience, Children s Hospital and Harvard Medical School, Boston, MA 02115, USA
Eur J Neurosci 19:2669-81. 2004
..These data suggest the existence of a homeostatic negative feedback loop in which increases in neuronal activity are damped by release of adenosine following activation of glutamate receptors...
- Light-induced changes in glutamate release from isolated rat retina is regulated by cyclic guanosine monophosphate
Department of Neurochemistry, Insitute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary
J Neurosci Res 67:149-55. 2002
..Exposure of the retina to the guanylyl cyclase inhibitor LY83583 (30 and 100 microM) showed fast, transient responses characterized by peaks at 90% +/- 1% and 80% +/- 3%, respectively...
- Nitrovasodilator responses in pulmonary arterioles from rats with nitrofen-induced congenital diaphragmatic hernia
The Division of Pediatric Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA
J Pediatr Surg 40:1706-11. 2005
- Effects of type-selective phosphodiesterase inhibitors on glucose-induced insulin secretion and islet phosphodiesterase activity
R Shafiee Nick
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow
Br J Pharmacol 115:1486-92. 1995
..9 These data are consistent with the presence of a type III PDE in rat islets of Langerhans...
- Role of nitric oxide and guanosine 3',5'-cyclic monophosphate in mediating nonadrenergic, noncholinergic relaxation in guinea-pig pulmonary arteries
S F Liu
Department of Thoracic Medicine, National Heart and Lung Institute, London
Br J Pharmacol 107:861-6. 1992
..10. These results suggest that NO may be released from intramural nerve endings other than adrenergic nerves (probably NANC nerves), and this leads to vasodilatation via activation of guanylyl cyclase...
- cGMP secreted from the tapeworm Hymenolepis diminuta is a signal molecule to the host intestine
Noah P Zimmerman
Department of Comparative Biosciences, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
J Parasitol 94:771-9. 2008
- Negative functional effects of natriuretic peptides are attenuated in hypertrophic cardiac myocytes by reduced particulate guanylyl cyclase activity
Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 088854 8021, USA
J Cardiovasc Pharmacol 49:100-5. 2007
..This blunted response was related to the reduced ability of natriuretic peptides to increase cyclic GMP levels due to a reduced stimulated particulate guanylyl cyclase activity...
- Inhaled agonists of soluble guanylate cyclase induce selective pulmonary vasodilation
Oleg V Evgenov
Department of Anesthesia and Critical Care, Massachusetts General Hospital, 55 Fruit Street, Gray Bigelow 444, Boston, MA 02114, USA
Am J Respir Crit Care Med 176:1138-45. 2007
..Nitric oxide-independent agonists of soluble guanylate cyclase (sGC) have been developed...
- Nitric oxide synthase and cGMP-mediated stimulation of renin secretion
C M Sayago
Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202, USA
Am J Physiol Regul Integr Comp Physiol 281:R1146-51. 2001
..04). This suggests that changes in endogenous cGMP production at levels not associated with renal hemodynamic changes are involved in a renin-stimulatory pathway. One source of this cGMP may be nNOS generation of NO in the kidney...
- The X-ray structure of the PurR-guanine-purF operator complex reveals the contributions of complementary electrostatic surfaces and a water-mediated hydrogen bond to corepressor specificity and binding affinity
M A Schumacher
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, Oregon 97201 3098, USA
J Biol Chem 272:22648-53. 1997
- Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases
Department of Chemistry, University of Utah, 315 South, 1400 East, Salt Lake City, Utah 84112, USA
Biochemistry 47:1043-50. 2008
..The differences in the activity of the various glycosylases for removal of FapyG and FapyA compared to OG in nonmutagenic versus promutagenic base pair contexts may serve to alter the mutagenic profiles of these lesions in vivo...
- Structural properties of the neutral and monoanionic forms of xanthosine, highly relevant to their substrate properties with various enzyme systems
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
Nucleosides Nucleotides Nucleic Acids 22:249-63. 2003
..These findings are highly relevant to the modes of binding, and to the substrate properties, of Xan, Xao and its 5'-phosphate (XMP) in numerous enzyme systems, hitherto virtually ignored, and illustrated by several concrete examples...
- Traceless solid-phase synthesis and biological evaluation of purine analogs as inhibitors of multidrug resistance protein 4
Theresa May Chin Tan
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597
J Comb Chem 9:210-8. 2007
..In the presence of 25 microM 15a or 17e, there was complete reversal. The reversal of resistance was achieved without any effects on the uptake and metabolism of 6-thioguanine...
- Neuronal nitric oxide synthase modulates basal catecholamine secretion in bovine chromaffin cells
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Spain
J Neurosci Res 69:327-40. 2002
..These results suggest that chromaffin cells exhibit a tonic production of NO by nNOS that keeps the basal CA secretion at low levels, and this could be necessary for maintaining a normotensive state...
- Cocaine self-administration by rats is inhibited by cyclic GMP-elevating agents: involvement of epigenetic markers
Laboratoire de Neurosciences Cognitives et Adaptatives, Universite de Strasbourg, Strasbourg, France
Int J Neuropsychopharmacol 16:1587-97. 2013
- Interactions at the dimer interface influence the relative efficiencies for purine nucleotide synthesis and pyrophosphorolysis in a phosphoribosyltransferase
University of North Carolina School of Pharmacy, Chapel Hill, NC 27599, USA
J Mol Biol 335:905-21. 2004
- Metallothioneins I/II are involved in the neuroprotective effect of sildenafil in focal brain injury
Institute of Biotechnology and Biomedicine, Universitat Autonoma de Barcelona, Spain
Neurochem Int 62:70-8. 2013
..Taken together these results indicate that cGMP-mediated pathways regulate expression of MT-I/II and support the involvement of these proteins in the neuroprotective effects of sildenafil in focal brain lesion...
- Inhibition of phosphodiesterases rescues striatal long-term depression and reduces levodopa-induced dyskinesia
Fondazione Santa Lucia, IRCCS, Via del Fosso di Fiorano 64, 00143, Rome, Italy
Brain 134:375-87. 2011
- Synthesis and evaluation of novel carbon-11 labeled oxopurine analogues for positron emission tomography imaging of translocator protein (18 kDa) in peripheral organs
Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4 9 1 Anagawa, Inage Ku, Chiba 263 8555, Japan
J Med Chem 54:6040-9. 2011
..PET with [(11)C]3a using a rat model of lung inflammation showed a significant signal in the lipopolysaccharide-treated lung...
- Fluorescence sensing of caffeine in aqueous solution with carbazole-based probe and imaging application in live cells
Ajit Kumar Mahapatra
Department of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711103, India
Bioorg Med Chem Lett 22:5379-83. 2012
..This new fluorescent probe with high sensitivity and selectivity for detection and first time imaging of caffeine in living cells was developed in aqueous media...
- Zaprinast activates MAPKs, NFκB, and Akt and induces the expressions of inflammatory genes in microglia
Heung Soon Lee
Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea
Int Immunopharmacol 13:232-41. 2012
..Although, zaprinast was found to have obvious effects on microglia, these were weaker than the effects of LPS...
- 5-HT7 receptor-mediated relaxation of the oviduct in nonpregnant proestrus pigs
Department of Pharmacology, School of Veterinary Medicine, Rakuno Gakuen University, 582 Bunkyodai Midorimachi, Ebetsu, Hokkaido 069 8501, Japan
Eur J Pharmacol 461:207-18. 2003
..The strongest relaxation through 5-HT(7) receptor activation suggests that 5-HT plays an important physiological role in the regulation of porcine oviduct contractility...
- The effect of chronic renal failure on phosphodiesterase inhibitor-induced relaxation responses in rabbit cavernosal strips
Department of Urology, Faculty of Medicine, University of Cumhuriyet, 58140 Sivas, Turkey
Eur J Pharmacol 462:155-60. 2003
..These results suggest that the decreased production or availability of endogenous nitric oxide in chronic renal failure animals leads to decreased efficacy of phosphodiesterase 5 inhibitors to induce relaxation...
- Functional significance of four successive glycine residues in the pyrophosphate binding loop of fungal 6-oxopurine phosphoribosyltransferases
IBGC, Universite de Bordeaux, UMR 5095, F 33000 Bordeaux, France
Protein Sci 21:1185-96. 2012
..Mutations affecting the enzyme activity or the previously characterized feedback inhibition by GMP are located at the nucleotide binding site and the dimer interface...
- Glucose concentration-dependent potentiation of insulin secretion by a new chemical entity, KCP256
Drug Discovery Research Laboratories, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co, Ltd, 1188 Shimotogari, Nagaizumi cho, Shizuoka, Japan
Eur J Pharmacol 528:176-82. 2005
..Since the insulinotropic activity of KCP256 only occurs at high concentrations of glucose, this novel drug may exhibit a decreased risk of drug-induced hypoglycemia compared with sulfonylurea drugs when treating patients with diabetes...
- Agonist activation of the G protein-coupled receptor GPR35 involves transmembrane domain III and is transduced via Gα₁₃ and β-arrestin-2
Molecular Pharmacology Group, Neuroscience and Molecular Pharmacology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK
Br J Pharmacol 162:733-48. 2011
..GPR35 is a poorly characterized G protein-coupled receptor at which kynurenic acid has been suggested to be the endogenous ligand. We wished to test this and develop assays appropriate for the study of this receptor...
- G-protein-coupled receptor 35 is a target of the asthma drugs cromolyn disodium and nedocromil sodium
Department of Metabolic Disorders, Amgen San Francisco, South San Francisco, CA 94080, USA
Pharmacology 86:1-5. 2010
..These findings suggest that GPR35 may play an important role in mast cell biology and be a potential target for the treatment of asthma...
- Nitric oxide and prostaglandins potentiate the liver regeneration cascade
Jodi M Schoen Smith
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg
Can J Gastroenterol 20:329-34. 2006
..These results also provide support for the hypothesis that NO and PGs are possible therapeutic targets to potentiate liver regeneration following surgical resection...
- Zaprinast attenuates hypoxic pulmonary artery injury and causes less aortic relaxation than milrinone
Ben M Tsai
Department of Surgery, Indiana University Medical Center, Indiana 46202, USA
Shock 24:417-20. 2005
..Therefore, PDE-5 inhibition may be advantageous in the treatment of pulmonary hypertension...
- Structures for the potential drug target purine nucleoside phosphorylase from Schistosoma mansoni causal agent of schistosomiasis
Humberto D Muniz Pereira
Centro de Biotecnologia Molecular Estrutural, Instituto de Fisica de Sao Carlos, Universidade de Sao Paulo, CP 369, CEP 13560 970, Sao Carlos SP, Brazil
J Mol Biol 353:584-99. 2005
..Residue Y202, which replaces F200 in human PNP, is able to reach over the ribose-binding site to interact with H259 and is predicted to form an additional hydrogen bond with the 5' hydroxyl of nucleoside substrates...
- Synthesis, biological testing, and binding mode prediction of 6,9-diarylpurin-8-ones as p38 MAP kinase inhibitors
Dominik R J Hauser
Department of Pharmaceutical and Medicinal Chemistry, Eberhard Karls University Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
J Med Chem 50:2060-6. 2007
..The presented results may form a solid basis for further optimization cycles since our theoretical findings are consistent with our experimental binding data and supported by the literature...
- Synthesis and incorporation into DNA fragments of the artificial nucleobase, 2-amino-8-oxopurine
Unite de Chimie Organique, URA CNRS 2128, Institut Pasteur, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France
Bioorg Med Chem Lett 15:1069-73. 2005
..The results obtained can be interpreted by the base pairing schemes involving the two edges of dJ depending on the anti and syn orientations...
- Synthesis and cardiovascular activity of new 8-alkylamino-1,3-dimethyl-7-(2-hydroxy-3- piperazinopropyl)-3,7-dihydro-1H-purine-2,6-diones
Department of Pharmaceutical Chemistry, Collegium Medicum, Jagiellonian University, Medyczna 9, PL 30 688 Krakow, Poland
Pol J Pharmacol 56:755-66. 2004
..All the new derivatives (11-17) and 2 showed a weak affinity for alpha1-(Ki = 0.225-1.400 microM) and alpha2-(Ki = 0.152-4.299 microM) receptors...
- Analysis of vasodilator responses to peroxynitrite in the hindlimb vascular bed of the cat
Bobby D Nossaman
Department of Anesthesiology, Ochsner Health System, New Orleans, Louisiana, USA
J Cardiovasc Pharmacol 50:358-66. 2007
..These studies suggest that under physiologic conditions, the cytotoxic effects of (ONOO-) on a short-term basis may have been overemphasized...
- Synthesis and SAR studies of trisubstituted purinones as potent and selective adenosine A2A receptor antagonists
Pharmacopeia, Inc, PO Box 5350, Princeton, NJ 08543, USA
Bioorg Med Chem Lett 19:1399-402. 2009
A series of trisubstituted purinones was synthesized and evaluated as A(2A) receptor antagonists...
- Selective inhibition of purified human phosphodiesterase 4A expressed in yeast cell GL62 by ciclamilast, piclamilast, and rolipram
Jun Chun Chen
Respiratory Drugs Research Laboratory of State Food and Drugs Administration of China, Medical School of Zhejiang University, Hangzhou 310031, China
Acta Pharmacol Sin 25:1171-5. 2004
- Phosphodiesterase 5 restricts NOS3/Soluble guanylate cyclase signaling to L-type Ca2+ current in cardiac myocytes
Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA
J Mol Cell Cardiol 47:304-14. 2009
..Our data suggests a novel physiological role for PDE5 in restricting the effects of NOS3/sGC/PKG signaling pathway to modulating beta-AR stimulated I(Ca), while limiting effects on cardiac contraction...
- Simultaneous electrochemical monitoring of metabolites related to the xanthine oxidase pathway using a grinded carbon electrode
Institute of Biophysics, Academy of Sciences of the Czech Republic, v v i, Kralovopolska 135, CZ 612 65 Brno, Czech Republic
Anal Chem 81:4302-7. 2009
..In addition, we show that the proposed electrochemical technique can be applied to parallel detection of metabolites involved in the XO pathway excreted in urine without any pretreatment of the clinical samples...
- 2-Phenylimidazo[2,1-i]purin-5-ones: structure-activity relationships and characterization of potent and selective inverse agonists at Human A3 adenosine receptors
University of Bonn, Pharmaceutical Institute Poppelsdorf, Kreuzbergweg 26, D 53115 Bonn, Germany
Bioorg Med Chem 11:347-56. 2003
..Due to their high A(3) affinity, selectivity, and relatively high water-solubility, 2-phenyl-imidazo[2,1-i]purin-5-ones may become useful research tools...
- Sildenafil protects epithelial cell through the inhibition of xanthine oxidase and the impairment of ROS production
Dipartimento di Oncologia Sperimentale e Applicazioni Cliniche, Sezione di Biochimica e Oncologia Clinica, AOUP Paolo Giaccone, Universita di Palermo, Via del Vespro 129, 90127 Palermo, Italy
Free Radic Res 44:232-9. 2010
- The effects of selective phosphodiesterase III and V inhibitors on adrenergic and non-adrenergic, non-cholinergic relaxation responses of guinea-pig pulmonary arteries
Department of Pharmacology, Akdeniz University Faculty of Medicine, Dekanlik Binasi, 07070 Arapsuyu, Antalya, Turkey
Auton Autacoid Pharmacol 23:117-24. 2003
..The combination of PDE III or V inhibitors with vasorelaxant drugs may be a hopeful approach for the treatment of pulmonary hypertension...
- Mechanism of nicotine-evoked release of 3H-noradrenaline in human cerebral cortex slices
Ran Sook Woo
Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School, Chonju 561 180, Republic of Korea
Br J Pharmacol 137:1063-70. 2002
- Peroxynitrite reacts with 8-nitropurines to yield 8-oxopurines
Joseph M Lee
Division of Bioengineering and Environmental Health and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Chem Res Toxicol 15:7-14. 2002
- Spontaneous photo-relaxation of urethral smooth muscle from sheep, pig and rat and its relationship with nitrergic neurotransmission
Department of Physiology, Faculty of Veterinary Sciences, Complutense University, Madrid, Spain
J Physiol 522:443-56. 2000
- Adenosine transporters in bloodstream forms of Trypanosoma brucei brucei: substrate recognition motifs and affinity for trypanocidal drugs
H P De Koning
Research School of Biosciences, University of Kent at Canterbury, Canterbury, Kent, UK
Mol Pharmacol 56:1162-70. 1999
- Impaired cerebral vasodilator responses to NO and PDE V inhibition after subarachnoid hemorrhage
C G Sobey
Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3052, Australia
Am J Physiol 277:H1718-24. 1999
..Thus an increased rate of cGMP hydrolysis by PDE V may be a major factor contributing to the impairment of NO-mediated cerebral vasodilatation after SAH...
- Pyrido[2,1-f]purine-2,4-dione derivatives as a novel class of highly potent human A(3) adenosine receptor antagonists
Eva Maria Priego
Instituto de Quimica Medica CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
J Med Chem 45:3337-44. 2002
..Because xanthine derivatives have traditionally been considered poor A(3) antagonists, the described pyrido[2,1-f]purine-2,4-dione derivatives represent a new family of adenosine receptor antagonists which deserves further exploration...
- Prolonged pulmonary vasodilator action of inhaled nitric oxide by Zaprinast in awake lambs
Department of Anesthesia, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA
J Appl Physiol 78:1288-95. 1995
..A stable level of pulmonary vasodilation was demonstrated in four additional lambs by combining intermittent NO breathing with an intravenous infusion of Zaprinast...
- Phosphodiesterase 3 inhibitors suppress oocyte maturation and consequent pregnancy without affecting ovulation and cyclicity in rodents
Department of Pharmacology, N V Organon, P O Box 20, 5340 BH Oss, The Netherlands
J Clin Invest 102:532-7. 1998
- Autoregulation of nitric oxide-soluble guanylate cyclase-cyclic GMP signalling in mouse thoracic aorta
M B Hussain
Wolfson Institute for Biomedical Research, University College London, The Rayne Institute, 5 University Street, London WC1E 6JJ, U K
Br J Pharmacol 128:1082-8. 1999
..These alterations in the sensitivity of the sGC - cyclic GMP pathway might represent a mechanism for the dynamic regulation of NO bioactivity...
- 3',5'-cyclic guanosine monophosphate activates mitogen-activated protein kinase in rat pinealocytes
A K Ho
Department of Physiology, Faculty of Medicine, University of Alberta, Edmonton, Canada
J Neurochem 73:598-604. 1999
..Our results indicate that, in this neuroendocrine tissue, the cGMP/PKG signaling pathway is an important mechanism used by hormones and neurotransmitters in activating MAPK...
- Relaxation and potentiation of cGMP-mediated response by ibudilast in bovine tracheal smooth muscle
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5 9 1 Shirokane, Minato ku, Tokyo 108 8641, Japan
Naunyn Schmiedebergs Arch Pharmacol 366:262-9. 2002
..However, ibudilast potentiates relaxation responses to ANP and SNP by inhibition of PDE 5, not by blockade of Ca(2+) channels. The enhancement of cGMP-mediated response may contribute to the therapeutic effects of ibudilast...
- Phosphodiesterase inhibitor-mediated potentiation of adenovirus delivery to myocardium
Institute of Molecular Cardiobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Mol Cell Cardiol 33:575-80. 2001
..Co-administration of phosphodiesterase-5 inhibitors and VEGF caused a synergistic increase in gene delivery. These results can be readily applied to existing models to further optimize vector delivery for gene therapy...
- Synthesis and benzodiazepine receptor binding activity of 2, 9-disubstituted quinolino[2', 3'-5, 4](3-pyrazolino)[3, 2-b]purin-4-ones
Ola A El-Sayed
Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Alexandria, Egypt
Arch Pharm (Weinheim) 335:207-12. 2002
..Compound 5c caused 83 +/- 8 %inhibition in [(3)H]R015-1788 specific benzodiazepine receptor binding followed by compounds 5f, 5h, and 5i while other analogs were inactive at 10 microM concentration...
- Purine nucleoside phosphorylase. 1. Structure-function studies
M D Erion
Central Research Laboratory, Ciba Geigy Ltd, Basel, Switzerland
Biochemistry 36:11725-34. 1997
..D., et al. (1997) Biochemistry 36, 11735-11748] and the use of mutagenesis to reverse the PNP substrate specificity from 6-oxopurines to 6-aminopurines [Stoeckler, J. D., et al. (1997) Biochemistry 36, 11749-11756]...
- Pulmonary effects of type V cyclic GMP specific phosphodiesterase inhibition in the anaesthetized guinea-pig
N C Turner
SmithKline Beecham Pharmaceuticals, The Frythe, Welwyn, Herts
Br J Pharmacol 111:1198-204. 1994
- Structural basis of the substrate specificity of Bacillus cereus adenosine phosphorylase
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853 1301, USA
Acta Crystallogr D Biol Crystallogr 68:239-48. 2012
..The mutation of Asp204 to asparagine led to a significant decrease in catalytic efficiency for adenosine without affecting the efficiency of inosine cleavage...
- 5-Nitro-2-(3-phenylpropylamino)benzoic acid is a GPR35 agonist
Discovery Biology Research, Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Inc, Taketoyo, Japan
Pharmacology 82:245-9. 2008
..These results suggest a novel pharmacological activity of NPPB and will provide useful information to search for more potent and selective GPR35 agonists...
- Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems
Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Poland
Eur J Biochem 269:4048-57. 2002
- cGMP stimulates renin secretion in vivo by inhibiting phosphodiesterase-3
William H Beierwaltes
Hypertension and Vascular Research Division, 7121 E and R Bldg, Henry Ford Hospital, Wayne State University, 2799 West Grand Blvd, Detroit, MI 48202, USA
Am J Physiol Renal Physiol 290:F1376-81. 2006
..The resulting increase in cAMP serves as an endogenous stimulus for renin secretion. This suggests a pathway by which NO can indirectly stimulate RSR through its second messenger cGMP...
- Changes in phosphodiesterase activity in the developing rat submandibular gland
Department of Pediatric Dentistry, School of Dentistry at Niigata, The Nippon Dental University, 1 8 Hamaura cho, Niigata 951 8580, Japan
Arch Oral Biol 47:567-76. 2002
..Expression of PDE5 was detected by inhibition studies, reverse transcriptase-polymerase chain reaction and Western blotting in the submandibular gland...
- Structures, ionization equilibria, and tautomerism of 6-oxopurines in solution
National Centre for Biological Sciences, GKVK Campus, Bellary Road, Bangalore 560065, India
J Phys Chem B 113:15101-18. 2009
..In general, deprotonation of the neutral molecule is marked by a downshift in the observed Raman wavenumbers, and protonation is accompanied by an upshift...
- Inhibition of hypoxanthine-guanine phosphoribosyltransferase by acyclic nucleoside phosphonates: a new class of antimalarial therapeutics
Dianne T Keough
The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 QLD, Australia
J Med Chem 52:4391-9. 2009
..These results provide a basis for the design of potent and selective ANP inhibitors of Pf HGXPRT as antimalarial drug leads...
- Activation of the nitric oxide-cGMP pathway reduces phasic contractions in neonatal rat bladder strips via protein kinase G
DEBRA E ARTIM
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
Am J Physiol Renal Physiol 297:F333-40. 2009
..These results suggest that the NO-cGMP-PKG pathway may be involved in inhibitory control of the neonatal rat bladder...
- Purine nucleoside phosphorylase. 2. Catalytic mechanism
M D Erion
Central Research Laboratory, Ciba Geigy Ltd, Basel, Switzerland mark erion gensia com
Biochemistry 36:11735-48. 1997
..Conservation of the catalytically important residues across nucleoside phosphorylases with specificity for 6-oxopurine nucleosides provided further support for the proposed catalytic mechanism...
- Xanthine, xanthosine and its nucleotides: solution structures of neutral and ionic forms, and relevance to substrate properties in various enzyme systems and metabolic pathways
Department of Biophysics, Institute of Experimental Physics, University of Warsaw, 93 Zwirki i Wigury, 02 089 Warszawa, Poland
Acta Biochim Pol 51:493-531. 2004
- Possible role of nitric oxide-cyclic GMP pathway in object recognition memory: effects of 7-nitroindazole and zaprinast
European Graduate School of Neuroscience EURON, Department of Psychiatry and Neuropsychology, Maastricht University, The Netherlands
Eur J Pharmacol 337:125-36. 1997
..Finally, since 7-nitroindazole affected mean arterial blood pressure it can not be regarded as a selective inhibitor of neuronal NO synthase...
- Unexpected non-Hoogsteen-based mutagenicity mechanism of FaPy-DNA lesions
Tim H Gehrke
Center for Integrated Protein Science at the Department of Chemistry, Ludwig Maximilians University, Munich, Germany
Nat Chem Biol 9:455-61. 2013
..The observed dG·dC→dT·dA transversion mutations are the result of base shifting and tautomerization...
- Low-dose phosphodiesterase inhibition improves responsiveness to inhaled nitric oxide in isolated lungs from endotoxemic rats
Department of Anaesthesiology, University of Heidelberg, Heidelberg, Germany
J Surg Res 138:224-30. 2007
..We investigated the efficacy of doses of PDE5 inhibitors that do not reduce pulmonary artery pressure alone (subthreshold doses) to improve the response to inhaled NO in an animal model of ALI...
- Role of phosphodiesterases in modulation of BKCa channels in hypertensive pulmonary arterial smooth muscle
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia 30912, USA
Ther Adv Respir Dis 2:119-27. 2008
- The neglected Pt-N(sulfonamido) bond in Pt chemistry. New fluorophore-containing Pt(II) complexes useful for assessing Pt(II) interactions with biomolecules
Anna Maria Christoforou
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
Inorg Chem 45:6771-81. 2006
..This stacking could explain the unprecedented, relatively low reactivity of a Pt complex bearing a dien-type ligand toward met vs 5'-GMP...
- Effects of dendroaspis natriuretic peptide on calcium-activated potassium current and its mechanism
Hui Shu Guo
Central Laboratory, First Affiliated Hospital of Dalian Medical Universty, Dalian, China
J Physiol Sci 58:1-6. 2008
..In conclusion, our results suggest that DNP increases I K(Ca) in gastric antral circular SMCs by increasing cGMP production and activating IP3Rs...
- Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35
Discovery Biology Research, Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Inc, 5 2 Taketoyo, Aichi 470 2393, Japan
FEBS Lett 580:5003-8. 2006
..These findings will facilitate the research on GPR35 and the drug discovery of the GPR35 modulators...
- Evaluation of the effect of phosphodiesterase on equine platelet activation and the effect of antigen challenge on platelet phosphodiesterase activity in horses with recurrent airway obstruction
Department of Veterinary Clinical Sciences, The Royal Veterinary College, North Mymms, Herts AL9 7TA, England
Am J Vet Res 71:534-40. 2010
- Comparative in vitro and in vivo studies on long-wavelength photosensitizers derived from bacteriopurpurinimide and Bacteriochlorin p6: fused imide ring enhances the in vivo PDT efficacy
Medicinal Chemistry Division, PDT Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
Bioconjug Chem 18:1460-73. 2007
..In contrast to methyl pyropheophorbide-a, the ester functionalities in bacteriopurpurinimide did not convert into the corresponding carboxylic acid by the enzyme esterases...
- Effects of phosphodiesterase V inhibition on nitric oxide-mediated relaxation responses in guinea pig trachea
Başak I Tuncel
Department of Pharmacology, Akdeniz University Faculty of Medicine, Arapsuyu, Antalya, Turkey
Pharmacology 71:102-6. 2004
..In conclusion, these data support the hypothesis that NO is a mediator of NANC relaxations of guinea pig tracheal rings and PDE V inhibition potentiates NO-mediated relaxation...
- Zaprinast, an inhibitor of cGMP-selective phosphodiesterases, enhances the secretion of TNF-alpha and IL-1beta and the expression of iNOS and MHC class II molecules in rat microglial cells
Sang Hyun Choi
Department of Pharmacology, Korea University College of Medicine, Sungbuk Gu, Seoul, South Korea
J Neurosci Res 67:411-21. 2002
..Summarizing, zaprinast, which is associated with cGMP/protein kinase G signaling, may augment central immune/inflammatory reactions, possibly via the increased production of TNF-alpha and IL-1beta by activated microglial cells...
- An intact medial preoptic area is necessary for zaprinast to modulate paced mating behavior in female rats
Sarah H Meerts
Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH 03755, United States
Physiol Behav 105:264-8. 2012
..These results demonstrate that the alterations in paced mating behavior observed in rats with mPOA lesions persist despite manipulation of the nitric oxide-cyclic guanosine monophospate pathway...