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[PMID]:26701297
[Au] Autor:Pal Choudhuri S; Delay RJ; Delay ER
[Ad] Endereço:Department of Biology and Vermont Chemosensory Group, Marsh Life Science, 109 Carrigan Drive, The University of Vermont, Burlington, VT 05405, United States. Electronic address: spalchou@uvm.edu.
[Ti] Título:Metabotropic glutamate receptors are involved in the detection of IMP and L-amino acids by mouse taste sensory cells.
[So] Source:Neuroscience;316:94-108, 2016 Mar 01.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:G-protein-coupled receptors are thought to be involved in the detection of umami and L-amino acid taste. These include the heterodimer taste receptor type 1 member 1 (T1r1)+taste receptor type 1 member 3 (T1r3), taste and brain variants of mGluR4 and mGluR1, and calcium sensors. While several studies suggest T1r1+T1r3 is a broadly tuned lLamino acid receptor, little is known about the function of metabotropic glutamate receptors (mGluRs) in L-amino acid taste transduction. Calcium imaging of isolated taste sensory cells (TSCs) of T1r3-GFP and T1r3 knock-out (T1r3 KO) mice was performed using the ratiometric dye Fura 2 AM to investigate the role of different mGluRs in detecting various L-amino acids and inosine 5' monophosphate (IMP). Using agonists selective for various mGluRs such as (RS)-3,5-dihydroxyphenylglycine (DHPG) (an mGluR1 agonist) and L-(+)-2-amino-4-phosphonobutyric acid (l-AP4) (an mGluR4 agonist), we evaluated TSCs to determine if they might respond to these agonists, IMP, and three L-amino acids (monopotassium L-glutamate, L-serine and L-arginine). Additionally, we used selective antagonists against different mGluRs such as (RS)-L-aminoindan-1,5-dicarboxylic acid (AIDA) (an mGluR1 antagonist), and (RS)-α-methylserine-O-phosphate (MSOP) (an mGluR4 antagonist) to determine if they can block responses elicited by these L-amino acids and IMP. We found that L-amino acid- and IMP-responsive cells also responded to each agonist. Antagonists for mGluR4 and mGluR1 significantly blocked the responses elicited by IMP and each of the L-amino acids. Collectively, these data provide evidence for the involvement of taste and brain variants of mGluR1 and mGluR4 in L-amino acid and IMP taste responses in mice, and support the concept that multiple receptors contribute to IMP and L-amino acid taste.
[Mh] Termos MeSH primário: Aminoácidos/metabolismo
Cálcio/metabolismo
Nucleotídeos de Inosina/metabolismo
Receptores de Glutamato Metabotrópico/metabolismo
Células Receptoras Sensoriais/efeitos dos fármacos
Papilas Gustativas/citologia
Percepção Gustatória/fisiologia
[Mh] Termos MeSH secundário: Análise de Variância
Animais
Relação Dose-Resposta a Droga
Fármacos atuantes sobre Aminoácidos Excitatórios/farmacologia
Feminino
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Masculino
Camundongos
Camundongos Transgênicos
Receptores Acoplados a Proteínas-G/genética
Receptores Acoplados a Proteínas-G/metabolismo
Percepção Gustatória/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Amino Acids); 0 (Excitatory Amino Acid Agents); 0 (Inosine Nucleotides); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Metabotropic Glutamate); 0 (taste receptors, type 1); 147336-22-9 (Green Fluorescent Proteins); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151225
[St] Status:MEDLINE


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[PMID]:24155207
[Au] Autor:Haishima Y; Kawakami T; Hasegawa C; Tanoue A; Yuba T; Isama K; Matsuoka A; Niimi S
[Ad] Endereço:Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
[Ti] Título:Screening study on hemolysis suppression effect of an alternative plasticizer for the development of a novel blood container made of polyvinyl chloride.
[So] Source:J Biomed Mater Res B Appl Biomater;102(4):721-8, 2014 May.
[Is] ISSN:1552-4981
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study is to identify a plasticizer that is effective in the suppression of the autohemolysis of the stored blood and can be used to replace di(2-ethylhexyl) phthalate (DEHP) in blood containers. The results of hemolysis test using mannitol-adenine-phosphate/red cell concentrates (MAP/RCC) spiked with plasticizers included phthalate, phthalate-like, trimeliate, citrate, and adipate derivatives revealed that di-isononyl-cyclohexane-1,2-dicarboxylate (Hexamoll(®) DINCH), di(2-ethylhexyl)-1,2,3,6-tetrahydro-phthalate (DOTP), and diisodecyl phthalate (DIDP) exhibited a hemolysis suppression effect almost equal to that of DEHP, but not other plasticizers. This finding suggested that the presence of 2 carboxy-ester groups at the ortho position on a 6-membered ring of carbon atoms may be required to exhibit such an effect. The hemolytic ratios of MAP/RCC-soaked polyvinyl chloride (PVC) sheets containing DEHP or different amounts of DINCH or DOTP were reduced to 10.9%, 9.2-12.4%, and 5.2-7.8%, respectively (MAP/RCC alone, 28.2%) after 10 weeks of incubation. The amount of plasticizer eluted from the PVC sheet was 53.1, 26.1-36.5, and 78.4-150 µg/mL for DEHP, DINCH, and DOTP, respectively. PVC sheets spiked with DIDP did not suppress the hemolysis induced by MAP/RCC because of low leachability (4.8-6.0 µg/mL). These results suggested that a specific structure of the plasticizer and the concentrations of least more than ∼10 µg/mL were required to suppress hemolysis due to MAP/RCC.
[Mh] Termos MeSH primário: Preservação de Sangue/instrumentação
Hemólise/efeitos dos fármacos
Plastificantes/farmacologia
Cloreto de Polivinila
[Mh] Termos MeSH secundário: Adenina
Benzoatos/farmacologia
Citratos
Ácidos Cicloexanocarboxílicos/farmacologia
Depressão Química
Ácidos Dicarboxílicos/farmacologia
Dietilexilftalato/farmacologia
Dietilexilftalato/toxicidade
Cromatografia Gasosa-Espectrometria de Massas
Glucose
Heparina
Seres Humanos
Nucleotídeos de Inosina/farmacologia
Manitol
Oxazóis/farmacologia
Plastificantes/química
Pirimidinonas/farmacologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoates); 0 (Citrates); 0 (Cyclohexanecarboxylic Acids); 0 (Dicarboxylic Acids); 0 (Inosine Nucleotides); 0 (Oxazoles); 0 (Plasticizers); 0 (Pyrimidinones); 0 (deoxyinosine diphosphate); 0 (diisononyl 1,2-cyclohexanedicarboxylic acid); 123495-11-4 (2,3-dihydro-5H-oxazolo(3,2-a)thieno(3,2-d)pyrimidin-5-one); 3OWL53L36A (Mannitol); 51404-37-6 (citrate phosphate dextrose); 9002-86-2 (Polyvinyl Chloride); 9005-49-6 (Heparin); 9GPJ04URH3 (trioctyl trimellitate); C42K0PH13C (Diethylhexyl Phthalate); IY9XDZ35W2 (Glucose); JAC85A2161 (Adenine)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131025
[St] Status:MEDLINE
[do] DOI:10.1002/jbm.b.33052


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[PMID]:24177564
[Au] Autor:Oka N; Morita Y; Itakura Y; Ando K
[Ad] Endereço:Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. oka@gifu-u.ac.jp.
[Ti] Título:Synthesis of inosine 6-phosphate diesters via phosphitylation of the carbonyl oxygen.
[So] Source:Chem Commun (Camb);49(98):11503-5, 2013 Dec 21.
[Is] ISSN:1364-548X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Inosine derivatives bearing a phosphodiester group at the O(6)-position of the nucleobase were synthesized via phosphitylation of the carbonyl oxygen using phosphoramidites activated by non-nucleophilic acidic activators.
[Mh] Termos MeSH primário: Nucleotídeos de Inosina/química
[Mh] Termos MeSH secundário: Aziridinas/química
Ésteres/química
Hipoxantina/química
Mesilatos/química
Oxigênio/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aziridines); 0 (Esters); 0 (Inosine Nucleotides); 0 (Mesylates); 2TN51YD919 (Hypoxanthine); S88TT14065 (Oxygen)
[Em] Mês de entrada:1406
[Cu] Atualização por classe:131115
[Lr] Data última revisão:
131115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131102
[St] Status:MEDLINE
[do] DOI:10.1039/c3cc46617e


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[PMID]:23288168
[Au] Autor:Ohta M; Toyama K; Gutterman DD; Campbell WB; Lemaître V; Teraoka R; Miura H
[Ad] Endereço:Department of Medicine and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
[Ti] Título:Ecto-5'-nucleotidase, CD73, is an endothelium-derived hyperpolarizing factor synthase.
[So] Source:Arterioscler Thromb Vasc Biol;33(3):629-36, 2013 Mar.
[Is] ISSN:1524-4636
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Adenosine dilates human coronary arteries by activating potassium channels in an endothelial cell-independent manner. Cell surface ecto-5'-nucleotidase (CD73) rapidly dephosphorylates extracellular adenosine 5'-monophosphate to adenosine. We tested the hypothesis that coronary vasodilation to adenine nucleotides is mediated by an endothelial CD73-dependent, extracellular production of adenosine that acts as an endothelium-derived hyperpolarizing factor. METHODS AND RESULTS: Videomicroscopy showed that adenine nucleotides, but not inosine, potently dilated and hyperpolarized human coronary arteries independent of nitric oxide, prostacyclin, and classical endothelium-derived hyperpolarizing factors, whereas endothelial denudation, adenosine receptor antagonism, adenosine deaminase, or CD73 blockers reduced vasodilations. Liquid chromatography-electrospray ionization-mass spectrometry revealed adenosine accumulation in perfusates from arteries in the presence of adenosine 5'-diphosphate. CD73 was localized on the cell surface of endothelial cells, but not of vascular smooth muscle cells, and its deficiency suppressed vasodilation of mouse coronary arteries to adenine nucleotides and augmented vasodilation to adenosine. Adenosine dose-dependently dilated and hyperpolarized human coronary arteries to a similar extent as adenosine 5'-diphosphate. CONCLUSIONS: Coronary vasodilation to adenine nucleotides is associated with endothelial CD73-dependent production of extracellular adenosine that acts as an endothelium-derived hyperpolarizing factor by relaxing and hyperpolarizing underlying vascular smooth muscle cells via activating adenosine receptors. Thus, CD73 is a novel endothelium-derived hyperpolarizing factor synthase in human and mouse coronary arteries.
[Mh] Termos MeSH primário: 5´-Nucleotidase/metabolismo
Nucleotídeos de Adenina/farmacologia
Adenosina/metabolismo
Fatores Biológicos/metabolismo
Vasos Coronários/efeitos dos fármacos
Células Endoteliais/efeitos dos fármacos
Vasodilatação/efeitos dos fármacos
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: 5'-Nucleotidase/antagonistas & inibidores
5'-Nucleotidase/deficiência
5'-Nucleotidase/genética
Nucleotídeos de Adenina/metabolismo
Adenosina Desaminase/metabolismo
Animais
Cromatografia Líquida
Vasos Coronários/enzimologia
Relação Dose-Resposta a Droga
Células Endoteliais/enzimologia
Inibidores Enzimáticos/farmacologia
Feminino
Proteínas Ligadas por GPI/antagonistas & inibidores
Proteínas Ligadas por GPI/deficiência
Proteínas Ligadas por GPI/genética
Proteínas Ligadas por GPI/metabolismo
Seres Humanos
Nucleotídeos de Inosina/farmacologia
Masculino
Potenciais da Membrana
Camundongos
Camundongos Knockout
Microscopia de Vídeo
Músculo Liso Vascular/efeitos dos fármacos
Músculo Liso Vascular/metabolismo
Miócitos de Músculo Liso/efeitos dos fármacos
Miócitos de Músculo Liso/metabolismo
Antagonistas de Receptores Purinérgicos P1/farmacologia
Espectrometria de Massas por Ionização por Electrospray
Vasodilatadores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Adenine Nucleotides); 0 (Biological Factors); 0 (Enzyme Inhibitors); 0 (GPI-Linked Proteins); 0 (Inosine Nucleotides); 0 (Purinergic P1 Receptor Antagonists); 0 (Vasodilator Agents); 0 (endothelium-dependent hyperpolarization factor); EC 3.1.3.5 (5'-Nucleotidase); EC 3.1.3.5 (NT5E protein, human); EC 3.1.3.5 (Nt5e protein, mouse); EC 3.5.4.4 (Adenosine Deaminase); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1304
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130105
[St] Status:MEDLINE
[do] DOI:10.1161/ATVBAHA.112.300600


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[PMID]:22422046
[Au] Autor:Ikeda T; Takasawa S; Noguchi N; Nata K; Yamauchi A; Takahashi I; Yoshikawa T; Sugawara A; Yonekura H; Okamoto H
[Ad] Endereço:Department of Biochemistry, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan. tikeda@kanazawa-med.ac.jp
[Ti] Título:Identification of a major enzyme for the synthesis and hydrolysis of cyclic ADP-ribose in amphibian cells and evolutional conservation of the enzyme from human to invertebrate.
[So] Source:Mol Cell Biochem;366(1-2):69-80, 2012 Jul.
[Is] ISSN:1573-4919
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cyclic ADP-ribose (cADPR), a metabolite of NAD(+), is known to function as a second messenger for intracellular Ca(2+) mobilization in various vertebrate and invertebrate tissues. In this study, we isolated two Xenopus laevis cDNAs (frog cd38 and cd157 cDNAs) homologous to the one encoding the human cADPR-metabolizing enzyme CD38. Frog CD38 and CD157 are 298-amino acid proteins with 35.9 and 27.2 % identity to human CD38 and CD157, respectively. Transfection of expression vectors for frog CD38 and CD157 into COS-7 cells revealed that frog CD38 had NAD(+) glycohydrolase, ADP-ribosyl cyclase (ARC), and cADPR hydrolase activities, and that frog CD157 had no enzymatic activity under physiological conditions. In addition, when recombinant CD38 and frog brain homogenate were electrophoresed on an SDS-polyacrylamide gel, ARC of the brain homogenate migrated to the same position in the gel as that of frog CD38, suggesting that frog CD38 is the major enzyme responsible for cADPR metabolism in amphibian cells. The frog cd38 gene consists of eight exons and is ubiquitously expressed in various tissues. These findings provide evidence for the existence of the CD38-cADPR signaling system in frog cells and suggest that the CD38-cADPR signaling system is conserved during vertebrate evolution.
[Mh] Termos MeSH primário: ADP-Ribosil Ciclase 1/genética
ADP-Ribosil Ciclase/genética
Antígenos CD/genética
ADP-Ribose Cíclica/biossíntese
Proteínas de Xenopus/genética
Xenopus laevis/genética
[Mh] Termos MeSH secundário: ADP-Ribosil Ciclase/biossíntese
ADP-Ribosil Ciclase/química
ADP-Ribosil Ciclase 1/biossíntese
ADP-Ribosil Ciclase 1/química
Sequência de Aminoácidos
Animais
Antígenos CD/biossíntese
Antígenos CD/química
Sequência de Bases
Encéfalo/enzimologia
Células COS
Cercopithecus aethiops
Clonagem Molecular
Sequência Conservada
ADP-Ribose Cíclica/metabolismo
Evolução Molecular
Proteínas Ligadas por GPI/biossíntese
Proteínas Ligadas por GPI/química
Proteínas Ligadas por GPI/genética
Seres Humanos
Hidrólise
Nucleotídeos de Inosina/química
Cinética
Dados de Sequência Molecular
NAD/análogos & derivados
NAD/química
Especificidade de Órgãos
Filogenia
Proteínas Recombinantes de Fusão/biossíntese
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/genética
Análise de Sequência de DNA
Proteínas de Xenopus/biossíntese
Proteínas de Xenopus/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD); 0 (GPI-Linked Proteins); 0 (Inosine Nucleotides); 0 (Recombinant Fusion Proteins); 0 (Xenopus Proteins); 0 (cyclic IDP-ribose); 0U46U6E8UK (NAD); 119340-53-3 (Cyclic ADP-Ribose); 22052-73-9 (nicotinamide-hypoxanthine dinucleotide); EC 3.2.2.5 (ADP-ribosyl Cyclase); EC 3.2.2.5 (ADP-ribosyl cyclase 2); EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
[Em] Mês de entrada:1210
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120317
[St] Status:MEDLINE
[do] DOI:10.1007/s11010-012-1284-0


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[PMID]:21519809
[Au] Autor:Minami S; Sato M; Shiraiwa Y; Iwamoto K
[Ad] Endereço:Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 985-8555, Japan.
[Ti] Título:Molecular characterization of adenosine 5'-monophosphate deaminase--the key enzyme responsible for the umami taste of nori (Porphyra yezoensis Ueda, Rhodophyta).
[So] Source:Mar Biotechnol (NY);13(6):1140-7, 2011 Dec.
[Is] ISSN:1436-2236
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The enzyme adenosine 5'-monophosphate deaminase (AMPD, EC 3.5.4.6) catalyzes the conversion of adenosine 5'-monophosphate to inosine 5'-mononucleotide (IMP). IMP is generally known as the compound responsible for the umami taste of the edible red alga Porphyra yezoensis Ueda that is known in Japan as nori. Therefore, we suspect that AMPD plays a key role in providing a favorable nori taste. In this study, we undertake the molecular characterization of nori-derived AMPD. The nori AMPD protein has a molecular mass of 55 kDa as estimated from both gel filtration and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The calculated molecular mass from the amino acid sequence deduced from cDNA is 57.1 kDa. The isoelectric point is 5.71. The coding region of AMPD consists of 1,566 bp encoding 522 amino acids and possesses a transmembrane domain and two N-glycosylation sites. The sequence identity of nori AMPD in human and yeast AMPDs was found to be less than 50% and 20% in DNA and amino acid sequences, respectively. Proline in the conserved motif of [SA]-[LIVM]-[NGS]-[STA]-D-D-P was found to be converted to glutamate. These results indicate that nori AMPD is a novel type of AMPD.
[Mh] Termos MeSH primário: AMP Desaminase/genética
Nucleotídeos de Inosina/química
Porphyra/enzimologia
Paladar
[Mh] Termos MeSH secundário: AMP Desaminase/isolamento & purificação
Sequência de Aminoácidos
Sequência de Bases
Cromatografia em Gel
Clonagem Molecular
Primers do DNA/genética
DNA Complementar/genética
Eletroforese em Gel de Poliacrilamida
Dados de Sequência Molecular
Análise de Sequência de DNA
Homologia de Sequência
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA Primers); 0 (DNA, Complementary); 0 (Inosine Nucleotides); EC 3.5.4.6 (AMP Deaminase)
[Em] Mês de entrada:1202
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110427
[St] Status:MEDLINE
[do] DOI:10.1007/s10126-011-9377-4


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[PMID]:21484439
[Au] Autor:Hübner M; Dizayee S; Matthes J; Seifert R; Herzig S
[Ad] Endereço:Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
[Ti] Título:Effect of MANT-nucleotides on L-type calcium currents in murine cardiomyocytes.
[So] Source:Naunyn Schmiedebergs Arch Pharmacol;383(6):573-83, 2011 Jun.
[Is] ISSN:1432-1912
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Membranous adenylyl cyclases play a major role in G-protein-coupled receptor signalling and regulate various cellular responses, such as cardiac contraction. Cardiac apoptosis and development of cardiac dysfunction is prevented in mice lacking AC 5, a predominant isoform in the heart. In the search for a potent and selective AC 5 inhibitor, we recently identified 2'(3')-methylanthraniloyl-inosine-5'-triphosphate(MANT-ITP) as the most potent AC 5 inhibitor with a K ( i ) of 13 nM. Therefore, AC inhibition of MANT-ITP was assessed in ventricular cardiomyocytes and compared to three other MANT-nucleotides to evaluate its effect on cardiac signalling. Basal and isoproterenol-induced L-type calcium currents (I (Ca,L)) in murine ventricular cardiomyocytes were recorded by whole-cell patch-clamp technique, using four different MANT-nucleotides. The effects of the MANT-nucleotides on I (Ca,L) were unexpectedly complex. All MANT-nucleotides exhibited an inhibitory effect on basal I (Ca,L). Additionally, several MANT-nucleotides, i.e., MANT-ITPγS, MANT-ATP, and MANT-ITP, caused a strong initial increase in basal I (Ca,L) within the first 2.5 min that appeared to be unrelated to AC 5 inhibition. However, we detected a significant reduction on isoproterenol-induced I (Ca,L) with MANT-ITP, supporting the notion that AC 5 plays an important role in agonist-stimulated activation of I (Ca,L). Collectively, MANT-nucleotides are useful tools for the characterization of recombinant ACs, for fluorescence studies and crystallography, but in intact cardiomyocytes, caution must be exerted since MANT-nucleotides apparently possess additional effects than AC 5 inhibition, limiting their usefulness as tools for intact cell studies.
[Mh] Termos MeSH primário: Inibidores de Adenilil Ciclase
Canais de Cálcio Tipo L/efeitos dos fármacos
Nucleotídeos de Inosina/farmacologia
Miócitos Cardíacos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Canais de Cálcio Tipo L/metabolismo
Inibidores Enzimáticos/farmacologia
Inosina Trifosfato/análogos & derivados
Inosina Trifosfato/farmacologia
Isoproterenol/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
Miócitos Cardíacos/metabolismo
Técnicas de Patch-Clamp
Receptores Acoplados a Proteínas-G/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adenylyl Cyclase Inhibitors); 0 (Calcium Channels, L-Type); 0 (Enzyme Inhibitors); 0 (Inosine Nucleotides); 0 (Receptors, G-Protein-Coupled); 132-06-9 (Inosine Triphosphate); L628TT009W (Isoproterenol)
[Em] Mês de entrada:1109
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110413
[St] Status:MEDLINE
[do] DOI:10.1007/s00210-011-0626-x


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[PMID]:21061651
[Au] Autor:Tiul'kova EI; Vataeva LA; Samoilov MO
[Ti] Título:[Effect of prenatal hypobaric hypoxia on activity of the rat brain phosphoinositide system].
[So] Source:Zh Evol Biokhim Fiziol;46(5):406-10, 2010 Sep-Oct.
[Is] ISSN:0044-4529
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Activity of the phosphoinositide system of the intracellular signalization was studied in offspring of rats exposed to severe hypobaric hypoxia at the 14-16th (group 1) or the 18-20th day (group 2) of prenatal development. At the age of 15 days, in animals of both experimental groups the basal level of triphosphoinositides in the brain cortex was shown to be elevated as compared with control. In the group 1 this parameters also remains elevated in adult animals. Application of glutamate produces a more pronounced increase of the inositephosphates in brain sections of the 15-day old rats of the group 1 than in sections of animals of the control group. In the 15-day old rats of the group 2, as compared with control, the phosphoinositide response to glutamate application was reduced. No changes in the inositephosphate levels were revealed after application of glutamate upon sections of adult (the 90-day old) control animals and of adult rats of the group 2. In sections of adult rats of the group 1, on the contrary, the glutamate application produced an increase of the inositephosphate content. The obtained data indicate essential changes of the phosphoinositide metabolism in the brain of rats exposed to action of hypoxia at the period of prenatal development. The character and the degree of these changes depend on the period of development when the action of hypoxia occurs.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Hipóxia/metabolismo
Nucleotídeos de Inosina/metabolismo
Efeitos Tardios da Exposição Pré-Natal/metabolismo
Sistemas do Segundo Mensageiro
[Mh] Termos MeSH secundário: Animais
Química Encefálica/efeitos dos fármacos
Feminino
Ácido Glutâmico/farmacologia
Hipóxia/complicações
Gravidez
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Inosine Nucleotides); 3KX376GY7L (Glutamic Acid)
[Em] Mês de entrada:1012
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:101111
[St] Status:MEDLINE


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[PMID]:20385596
[Au] Autor:Iyama T; Abolhassani N; Tsuchimoto D; Nonaka M; Nakabeppu Y
[Ad] Endereço:Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
[Ti] Título:NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest.
[So] Source:Nucleic Acids Res;38(14):4834-43, 2010 Aug.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nucleotides function in a variety of biological reactions; however, they can undergo various chemical modifications. Such modified nucleotides may be toxic to cells if not eliminated from the nucleotide pools. We performed a screen for modified-nucleotide binding proteins and identified human nucleoside diphosphate linked moiety X-type motif 16 (NUDT16) protein as an inosine triphosphate (ITP)/xanthosine triphosphate (XTP)/GTP-binding protein. Recombinant NUDT16 hydrolyzes purine nucleoside diphosphates to the corresponding nucleoside monophosphates. Among 29 nucleotides examined, the highest k(cat)/K(m) values were for inosine diphosphate (IDP) and deoxyinosine diphosphate (dIDP). Moreover, NUDT16 moderately hydrolyzes (deoxy)inosine triphosphate ([d]ITP). NUDT16 is mostly localized in the nucleus, and especially in the nucleolus. Knockdown of NUDT16 in HeLa MR cells caused cell cycle arrest in S-phase, reduced cell proliferation, increased accumulation of single-strand breaks in nuclear DNA as well as increased levels of inosine in RNA. We thus concluded that NUDT16 is a (deoxy)inosine diphosphatase that may function mainly in the nucleus to protect cells from deleterious effects of (d)ITP.
[Mh] Termos MeSH primário: Hidrolases Anidrido Ácido/metabolismo
Quebras de DNA de Cadeia Simples
Pirofosfatases/metabolismo
[Mh] Termos MeSH secundário: Hidrolases Anidrido Ácido/deficiência
Hidrolases Anidrido Ácido/genética
Sequência de Aminoácidos
Núcleo Celular/química
Proliferação Celular
Técnicas de Silenciamento de Genes
Guanosina Trifosfato/metabolismo
Células HeLa
Seres Humanos
Nucleotídeos de Inosina/metabolismo
Inosina Trifosfato/metabolismo
Dados de Sequência Molecular
Pirofosfatases/deficiência
Pirofosfatases/genética
Ribonucleotídeos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Inosine Nucleotides); 0 (Ribonucleotides); 132-06-9 (Inosine Triphosphate); 6253-56-1 (xanthosine 5'-triphosphate); 86-01-1 (Guanosine Triphosphate); EC 3.6.- (Acid Anhydride Hydrolases); EC 3.6.1.- (Nudt16 protein, human); EC 3.6.1.- (Pyrophosphatases); EC 3.6.1.- (inosine diphosphatase)
[Em] Mês de entrada:1009
[Cu] Atualização por classe:141203
[Lr] Data última revisão:
141203
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100414
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkq249


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[PMID]:20227382
[Au] Autor:Purdy MM; Holz-Schietinger C; Reich NO
[Ad] Endereço:Department of Chemistry and Biochemistry, University of California, Santa Barbara, 93106-9510, USA.
[Ti] Título:Identification of a second DNA binding site in human DNA methyltransferase 3A by substrate inhibition and domain deletion.
[So] Source:Arch Biochem Biophys;498(1):13-22, 2010 Jun 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human DNA methyltransferase 3A (DNMT3A) is essential for establishing DNA methylation patterns. Knowing the key factors involved in the regulation of mammalian DNA methylation is critical to furthering understanding of embryonic development and designing therapeutic approaches targeting epigenetic mechanisms. We observe substrate inhibition for the full length DNMT3A but not for its isolated catalytic domain, demonstrating that DNMT3A has a second binding site for DNA. Deletion of recognized domains of DNMT3A reveals that the conserved PWWP domain is necessary for substrate inhibition and forms at least part of the allosteric DNA binding site. The PWWP domain is demonstrated here to bind DNA in a cooperative manner with muM affinity. No clear sequence preference was observed, similar to previous observations with the isolated PWWP domain of Dnmt3b but with one order of magnitude weaker affinity. Potential roles for a low affinity, low specificity second DNA binding site are discussed.
[Mh] Termos MeSH primário: Domínio Catalítico
DNA (Citosina-5-)-Metiltransferases/química
DNA (Citosina-5-)-Metiltransferases/metabolismo
DNA/metabolismo
Inibidores Enzimáticos/farmacologia
Deleção de Sequência
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sequência de Bases
Bovinos
Sequência Conservada
DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores
DNA (Citosina-5-)-Metiltransferases/genética
Seres Humanos
Nucleotídeos de Inosina/química
Nucleotídeos de Inosina/farmacologia
Cinética
Dados de Sequência Molecular
Oligonucleotídeos/genética
Oligonucleotídeos/farmacologia
Polímeros/química
Estrutura Terciária de Proteína/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Inosine Nucleotides); 0 (Oligonucleotides); 0 (Polymers); 9007-49-2 (DNA); EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases); EC 2.1.1.37 (DNA methyltransferase 3A)
[Em] Mês de entrada:1006
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100316
[St] Status:MEDLINE
[do] DOI:10.1016/j.abb.2010.03.007



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