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Pesquisa : D12.776.157.530.400.400.100.500.500 [Categoria DeCS]
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[PMID]:29272360
[Au] Autor:Hasan MK; Friedman TC; Sims C; Lee DL; Espinoza-Derout J; Ume A; Chalfant V; Lee ML; Sinha-Hikim I; Lutfy K; Liu Y; Mahata SK; Sinha-Hikim AP
[Ad] Endereço:Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California.
[Ti] Título:α7-Nicotinic Acetylcholine Receptor Agonist Ameliorates Nicotine Plus High-Fat Diet-Induced Hepatic Steatosis in Male Mice by Inhibiting Oxidative Stress and Stimulating AMPK Signaling.
[So] Source:Endocrinology;159(2):931-944, 2018 02 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:α7-Nicotinic acetylcholine receptor (α7nAChR) agonists confer protection against a wide variety of cytotoxic insults and suppress oxidative stress and apoptosis in various cell systems, including hepatocytes. We recently demonstrated that nicotine, when combined with a high-fat diet (HFD), triggers oxidative stress, activates hepatocyte apoptosis, and exacerbates HFD-induced hepatic steatosis in male mice. This study evaluates whether PNU-282987 (PNU), a specific α7nAChR agonist, is effective in preventing nicotine plus HFD-induced hepatic steatosis. Adult C57BL6 male mice were fed a normal chow diet or HFD with 60% of calories derived from fat and received twice-daily intraperitoneal injections of 0.75 mg/kg body weight (BW) of nicotine, PNU (0.26 mg/kg BW), PNU plus nicotine, or saline for 10 weeks. PNU treatment was effective in attenuating nicotine plus HFD-induced increase in hepatic triglyceride levels, hepatocyte apoptosis, and hepatic steatosis. The preventive effects of PNU on nicotine plus HFD-induced hepatic steatosis were mediated by suppression of oxidative stress and activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) together with inhibition of its downstream target sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-coenzyme A-carboxylase (ACC). We conclude that the α7nAChR agonist PNU protects against nicotine plus HFD-induced hepatic steatosis in obese mice. PNU appears to work at various steps of signaling pathways involving suppression of oxidative stress, activation of AMPK, and inhibition of SREBP1c, FAS, and ACC. α7nAChR agonists may be an effective therapeutic strategy for ameliorating fatty liver disease, especially in obese smokers.
[Mh] Termos MeSH primário: Benzamidas/farmacologia
Compostos Bicíclicos com Pontes/farmacologia
Fígado Gorduroso/tratamento farmacológico
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Animais
Benzamidas/uso terapêutico
Compostos Bicíclicos com Pontes/uso terapêutico
Dieta Hiperlipídica/efeitos adversos
Fígado Gorduroso/etiologia
Fígado Gorduroso/metabolismo
Fígado Gorduroso/patologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Obesos
Nicotina/toxicidade
Transdução de Sinais/efeitos dos fármacos
Receptor Nicotínico de Acetilcolina alfa7/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Benzamides); 0 (Bridged Bicyclo Compounds); 0 (PNU-282987); 0 (alpha7 Nicotinic Acetylcholine Receptor); 6M3C89ZY6R (Nicotine); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00594


  2 / 2352 MEDLINE  
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[PMID]:29307828
[Au] Autor:Wang X; Min S; Xie F; Yang J; Li L; Chen J
[Ad] Endereço:Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
[Ti] Título:Glial cell-derived neurotrophic factor alleviates sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nicotinic acetylcholine receptors in an experimental rat model of neuromyopathy.
[So] Source:Biochem Biophys Res Commun;496(2):260-266, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sepsis-induced neuromuscular dysfunction results from up-regulation of the expression of γ- and α7-nicotinic acetylcholine receptors (nAChR). Although glial cell derived neurotrophic factor (GDNF) has been implicated in repairing and supporting neurons, little is known about the effects of GDNF on demyelination of nerves in sepsis. In this study, we tested the hypothesis that GDNF could alleviate sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nAChR in an experimental rat model of neuromyopathy. Rats were randomly divided into a sham group and a sepsis group. Levels of inflammatory factors, muscle function, and nicotinic acetylcholine receptors were tested in rats after cecal ligation and puncture (CLP). At 24 h after CLP, GDNF was injected around the sciatic nerve of sepsis rats, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining was used to detect the expression of nAChRs. GDNF and its downstream effector (Erk1/2 and GFR-α), neuregulin-1 (NRG-1) and γ- and α7-nAChR were measured using Western blot analysis. The expression of GDNF reached a minimum at 24 h after CLP. Compared with the sham group, the release of cytokines and the expression of γ- and α7-nAChR were significantly increased in the sepsis group. The administration of GDNF significantly alleviated sepsis-induced neuromuscular dysfunction, as well as reducing the expression of γ- and α7-nAChR. In addition, the expression of Erk1/2, GFR-α, NRG-1 were significantly increased after GDNF treatment. GDNF administration may improve patient outcomes by reducing the demyelination of nerves and the expression of γ- and α7-nAChR.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Doenças Desmielinizantes/tratamento farmacológico
Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia
Doenças Musculares/tratamento farmacológico
Fármacos Neuroprotetores/farmacologia
Sepse/tratamento farmacológico
Receptor Nicotínico de Acetilcolina alfa7/genética
[Mh] Termos MeSH secundário: Animais
Citocinas/genética
Citocinas/metabolismo
Doenças Desmielinizantes/genética
Doenças Desmielinizantes/metabolismo
Doenças Desmielinizantes/patologia
Modelos Animais de Doenças
Regulação da Expressão Gênica
Fatores de Troca do Nucleotídeo Guanina/genética
Fatores de Troca do Nucleotídeo Guanina/metabolismo
Masculino
Proteína Quinase 1 Ativada por Mitógeno/genética
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/genética
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Doenças Musculares/genética
Doenças Musculares/metabolismo
Doenças Musculares/patologia
Neuregulina-1/genética
Neuregulina-1/metabolismo
Junção Neuromuscular/efeitos dos fármacos
Junção Neuromuscular/metabolismo
Junção Neuromuscular/patologia
Isoformas de Proteínas/antagonistas & inibidores
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Ratos
Ratos Sprague-Dawley
Nervo Isquiático/efeitos dos fármacos
Nervo Isquiático/metabolismo
Nervo Isquiático/patologia
Sepse/genética
Sepse/metabolismo
Sepse/patologia
Transdução de Sinais
Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores
Receptor Nicotínico de Acetilcolina alfa7/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Cytokines); 0 (Glial Cell Line-Derived Neurotrophic Factor); 0 (Guanine Nucleotide Exchange Factors); 0 (Neuregulin-1); 0 (Neuroprotective Agents); 0 (Nrg1 protein, rat); 0 (Protein Isoforms); 0 (alpha7 Nicotinic Acetylcholine Receptor); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


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[PMID]:29261717
[Au] Autor:Elnagar MR; Walls AB; Helal GK; Hamada FM; Thomsen MS; Jensen AA
[Ad] Endereço:Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken, Copenhagen Ø, Denmark.
[Ti] Título:Probing the putative α7 nAChR/NMDAR complex in human and murine cortex and hippocampus: Different degrees of complex formation in healthy and Alzheimer brain tissue.
[So] Source:PLoS One;12(12):e0189513, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:α7 nicotinic acetylcholine receptors (nAChRs) and N-methyl-D-aspartate receptors (NMDARs) are key mediators of central cholinergic and glutamatergic neurotransmission, respectively. In addition to numerous well-established functional interactions between α7 nAChRs and NMDARs, the two receptors have been proposed to form a multimeric complex, and in the present study we have investigated this putative α7 nAChR/NMDAR assembly in human and murine brain tissues. By α-bungarotoxin (BGT) affinity purification, α7 and NMDAR subunits were co-purified from human and murine cortical and hippocampal homogenates, substantiating the notion that the receptors are parts of a multimeric complex in the human and rodent brain. Interestingly, the ratios between GluN1 and α7 levels in BGT pull-downs from cortical homogenates from Alzheimer's disease (AD) brains were significantly lower than those in pull-downs from non-AD controls, indicating a reduced degree of α7 nAChR/NMDAR complex formation in the diseased tissue. A similar difference in GluN1/α7 ratios was observed between pull-downs from cortical homogenates from adult 3xTg-AD and age-matched wild type (WT) mice, whereas the GluN1/α7 ratios determined in pull-downs from young 3xTg-AD and age-matched WT mice did not differ significantly. The observation that pretreatment with oligomeric amyloid-ß1-42 reduced GluN1/α7 ratios in BGT pull-downs from human cortical homogenate in a concentration-dependent manner provided a plausible molecular mechanism for this observed reduction. In conclusion, while it will be important to further challenge the existence of the putative α7 nAChR/NMDAR complex in future studies applying other methodologies than biochemical assays and to investigate the functional implications of this complex for cholinergic and glutamatergic neurotransmission, this work supports the formation of the complex and presents new insights into its regulation in healthy and diseased brain tissue.
[Mh] Termos MeSH primário: Doença de Alzheimer/metabolismo
Córtex Cerebral/metabolismo
Hipocampo/metabolismo
Receptores de N-Metil-D-Aspartato/metabolismo
Receptor Nicotínico de Acetilcolina alfa7/metabolismo
[Mh] Termos MeSH secundário: Adulto
Animais
Estudos de Casos e Controles
Feminino
Seres Humanos
Masculino
Camundongos
Camundongos Knockout
Meia-Idade
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, N-Methyl-D-Aspartate); 0 (alpha7 Nicotinic Acetylcholine Receptor)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189513


  4 / 2352 MEDLINE  
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[PMID]:29227073
[Au] Autor:Uspenska KR; Gergalova GL; Lykhmus OY; Skok MV
[Ti] Título:The effect of amixin and agmatine on cytochrome C release from isolated mitochondria
[So] Source:Ukr Biochem J;88(1):5-10, 2016 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:Mitochondrial nicotinic acetylcholine receptors (nAChRs) control permeability transition pore formation and cytochrome c release in the presence of apoptogenic factors. This study demonstrates that pharmacological agents amixin and agmatine affect mitochondrial nAChR functioning: they slightly suppress cytochrome c release from mouse brain and liver mitochondria stimulated with apoptogenic dose of Са2+ and prevent the effect of α7 nAChR agonist PNU282987. We conclude that mitochondria may be one of therapeutic targets of amixin and agmatine.
[Mh] Termos MeSH primário: Agmatina/farmacologia
Indutores de Interferon/farmacologia
Mitocôndrias/efeitos dos fármacos
Tilorona/farmacologia
Receptor Nicotínico de Acetilcolina alfa7/metabolismo
[Mh] Termos MeSH secundário: Animais
Benzamidas/antagonistas & inibidores
Benzamidas/farmacologia
Encéfalo/efeitos dos fármacos
Compostos Bicíclicos com Pontes/antagonistas & inibidores
Compostos Bicíclicos com Pontes/farmacologia
Cálcio/farmacologia
Fracionamento Celular
Citocromos c/antagonistas & inibidores
Citocromos c/secreção
Fígado/efeitos dos fármacos
Fígado/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Mitocôndrias/metabolismo
Agonistas Nicotínicos/farmacologia
Especificidade de Órgãos
Receptor Nicotínico de Acetilcolina alfa7/agonistas
Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamides); 0 (Bridged Bicyclo Compounds); 0 (Interferon Inducers); 0 (Nicotinic Agonists); 0 (PNU-282987); 0 (alpha7 Nicotinic Acetylcholine Receptor); 70J407ZL5Q (Agmatine); 9007-43-6 (Cytochromes c); O6W7VEW6KS (Tilorone); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.005


  5 / 2352 MEDLINE  
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[PMID]:29261656
[Au] Autor:Weed MR; Polino J; Signor L; Bookbinder M; Keavy D; Benitex Y; Morgan DG; King D; Macor JE; Zaczek R; Olson R; Bristow LJ
[Ad] Endereço:Genetically Defined Diseases and Genomics, Bristol-Myers Squibb Company, Wallingford, CT, United States of America.
[Ti] Título:Nicotinic alpha 7 receptor agonists EVP-6124 and BMS-933043, attenuate scopolamine-induced deficits in visuo-spatial paired associates learning.
[So] Source:PLoS One;12(12):e0187609, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Agonists at the nicotinic acetylcholine alpha 7 receptor (nAChR α7) subtype have the potential to treat cognitive deficits in patients with Alzheimer's disease (AD) or schizophrenia. Visuo-spatial paired associates learning (vsPAL) is a task that has been shown to reliably predict conversion from mild cognitive impairment to AD in humans and can also be performed by nonhuman primates. Reversal of scopolamine-induced impairment of vsPAL performance may represent a translational approach for the development of nAChR α7 agonists. The present study investigated the effect of treatment with the acetylcholinesterase inhibitor, donepezil, or three nAChR α7 agonists, BMS-933043, EVP-6124 and RG3487, on vsPAL performance in scopolamine-treated cynomolgus monkeys. Scopolamine administration impaired vsPAL performance accuracy in a dose- and difficulty- dependent manner. The impairment of eventual accuracy, a measure of visuo-spatial learning during the task, was significantly ameliorated by treatment with donepezil (0.3 mg/kg, i.m.), EVP-6124 (0.01 mg/kg, i.m.) or BMS-933043 (0.03, 0.1 and 0.3 mg/kg, i.m.). Both nAChR α7 agonists showed inverted-U shaped dose-effect relationships with EVP-6124 effective at a single dose only whereas BMS-933043 was effective across at least a 10 fold dose/exposure range. RG3487 was not efficacious in this paradigm at the dose range examined (0.03-1 mg/kg, i.m.). These results are the first demonstration that the nAChR α7 agonists, EVP-6124 and BMS-933043, can ameliorate scopolamine-induced cognitive deficits in nonhuman primates performing the vsPAL task.
[Mh] Termos MeSH primário: Aprendizagem por Associação de Pares/efeitos dos fármacos
Quinuclidinas/farmacologia
Percepção Espacial/classificação
Compostos de Espiro/farmacologia
Tiofenos/farmacologia
Percepção Visual/efeitos dos fármacos
Receptor Nicotínico de Acetilcolina alfa7/agonistas
[Mh] Termos MeSH secundário: Animais
Indanos/farmacologia
Macaca fascicularis
Masculino
Piperidinas/farmacologia
Quinuclidinas/química
Tempo de Reação/efeitos dos fármacos
Hidrobrometo de Escopolamina
Compostos de Espiro/química
Análise e Desempenho de Tarefas
Tiofenos/química
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (7-chloro-N-quinuclidin-3-yl-benzo(b)thiophene-2-carboxamide); 0 (BMS-933043); 0 (Indans); 0 (Piperidines); 0 (Quinuclidines); 0 (Spiro Compounds); 0 (Thiophenes); 0 (alpha7 Nicotinic Acetylcholine Receptor); 451IFR0GXB (Scopolamine Hydrobromide); 8SSC91326P (donepezil)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0187609


  6 / 2352 MEDLINE  
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[PMID]:29174812
[Au] Autor:Balsera B; Mulet J; Sala S; Sala F; de la Torre-Martínez R; González-Rodríguez S; Plata A; Naesens L; Fernández-Carvajal A; Ferrer-Montiel A; Criado M; Pérez de Vega MJ; González-Muñiz R
[Ad] Endereço:Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
[Ti] Título:Amino acid and peptide prodrugs of diphenylpropanones positive allosteric modulators of α7 nicotinic receptors with analgesic activity.
[So] Source:Eur J Med Chem;143:157-165, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:α7 Nicotinic acetylcholine receptors (nAChRs) are ion channels implicated in a number of CNS pathological processes, including pain and psychiatric, cognitive and inflammatory diseases. Comparing with orthosteric agonism, positive allosteric modulation of these channels constitutes an interesting approach to achieve selectivity versus other nicotinic receptors. We have recently described new chalcones and 1,3-diphenylpropanones as positive allosteric modulators (PAMs) of α7 nAChRs, which proved to have good analgesic activities but poor pharmacokinetic properties. Here we report the preparation of amino acid and peptide derivatives as prodrugs of these modulators with the aim of improving their in vivo biological activity. While the valine derivative showed very short half life in aqueous solutions to be considered a prodrug, Val-Val and Val-Pro-Val are suitable precursors of the parent 1,3-diphenylpropanones, via chemical and enzymatic transformation, respectively. Compounds 19 (Val-Val) and 21 (Val-Pro-Val), prodrugs of the 2',5',4-trihydroxy-1,3-diphenylpropan-1-one 3, showed significant antinociceptive activity in in vivo assays. The best compound, 21, displayed a better profile in the analgesia test than its parent compound 3, exhibiting about the same potency but long-lasting effects.
[Mh] Termos MeSH primário: Aminoácidos/farmacologia
Analgésicos/farmacologia
Dor/tratamento farmacológico
Peptídeos/farmacologia
Fenilpropionatos/farmacologia
Pró-Fármacos/farmacologia
Receptor Nicotínico de Acetilcolina alfa7/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica/efeitos dos fármacos
Aminoácidos/síntese química
Aminoácidos/química
Analgésicos/síntese química
Analgésicos/química
Animais
Relação Dose-Resposta a Droga
Edema/induzido quimicamente
Edema/tratamento farmacológico
Adjuvante de Freund
Seres Humanos
Inflamação/induzido quimicamente
Inflamação/tratamento farmacológico
Masculino
Estrutura Molecular
Medição da Dor
Peptídeos/síntese química
Peptídeos/química
Fenilpropionatos/síntese química
Fenilpropionatos/química
Pró-Fármacos/síntese química
Pró-Fármacos/química
Ratos
Ratos Wistar
Relação Estrutura-Atividade
Xenopus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2',5',4-trihydroxy-1,3-diphenylpropan-1-one); 0 (Amino Acids); 0 (Analgesics); 0 (Peptides); 0 (Phenylpropionates); 0 (Prodrugs); 0 (alpha7 Nicotinic Acetylcholine Receptor); 9007-81-2 (Freund's Adjuvant)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  7 / 2352 MEDLINE  
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[PMID]:28885019
[Au] Autor:Quadri M; Stokes C; Gulsevin A; Felts ACJ; Abboud KA; Papke RL; Horenstein NA
[Ad] Endereço:Department of Chemistry, University of Florida , P.O. Box 117200, Gainesville, Florida 32611-7200, United States.
[Ti] Título:Sulfonium as a Surrogate for Ammonium: A New α7 Nicotinic Acetylcholine Receptor Partial Agonist with Desensitizing Activity.
[So] Source:J Med Chem;60(18):7928-7934, 2017 Sep 28.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Weak partial agonists that promote a desensitized state of the α7 nicotinic acetylcholine receptor (nAChR) have been associated with anti-inflammatory effects. Exemplar compounds feature a tertiary or quaternary ammonium group. We report the synthesis, structure, and electrophysiological evaluation of 1-ethyl-4-phenylthiomorpholin-1-ium triflate, a weak partial agonist with a sulfonium isostere of the ammonium pharmacophore. These results offer new insights in understanding nAChR-ligand interactions and provide a new chemical space to target the α7 nAChR.
[Mh] Termos MeSH primário: Morfolinas/química
Morfolinas/farmacologia
Agonistas Nicotínicos/química
Agonistas Nicotínicos/farmacologia
Oniocompostos/química
Oniocompostos/farmacologia
Compostos de Sulfônio/química
Compostos de Sulfônio/farmacologia
Receptor Nicotínico de Acetilcolina alfa7/agonistas
[Mh] Termos MeSH secundário: Compostos de Amônio/síntese química
Compostos de Amônio/química
Compostos de Amônio/farmacologia
Animais
Seres Humanos
Modelos Moleculares
Morfolinas/síntese química
Agonistas Nicotínicos/síntese química
Oniocompostos/síntese química
Compostos de Sulfônio/síntese química
Xenopus laevis
Receptor Nicotínico de Acetilcolina alfa7/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-ethyl-4-phenylthiomorpholin-1-ium); 0 (Ammonium Compounds); 0 (Morpholines); 0 (Nicotinic Agonists); 0 (Onium Compounds); 0 (Sulfonium Compounds); 0 (alpha7 Nicotinic Acetylcholine Receptor)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00875


  8 / 2352 MEDLINE  
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[PMID]:28864899
[Au] Autor:Makarova YV; Shelukhina IV; Mukherjee AK; Kuznetsov DV; Tsetlin VI; Utkin YN
[Ad] Endereço:Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
[Ti] Título:Detection of human neuronal α7 nicotinic acetylcholine receptors by conjugates of snake α-neurotoxin with quantum dots.
[So] Source:Dokl Biochem Biophys;475(1):253-255, 2017 Jul.
[Is] ISSN:1608-3091
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:Fluorescent derivatives are widely used to study the structure and functions of proteins. Quantum dots (QDs), fluorescent semiconductor nanocrystals, have a high quantum yield and are much more resistant to bleaching compared to organic dyes. Conjugates of α-neurotoxins with QDs were used for visualization of human α7 acetylcholine receptors heterologously expressed in GH4C1 pituitary adenoma cells. Specific staining of cells by the conjugated toxins was observed.
[Mh] Termos MeSH primário: Neurotoxinas/química
Neurotoxinas/metabolismo
Pontos Quânticos/química
Venenos de Serpentes/química
Receptor Nicotínico de Acetilcolina alfa7/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Seres Humanos
Imagem Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurotoxins); 0 (Snake Venoms); 0 (alpha7 Nicotinic Acetylcholine Receptor)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE
[do] DOI:10.1134/S1607672917040032


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[PMID]:28842382
[Au] Autor:Koga M; Kanaoka Y; Sugiyama K; Ohishi K; Ejima Y; Hisanaga M; Kataoka Y; Yamauchi A
[Ad] Endereço:Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
[Ti] Título:Varenicline promotes endothelial cell migration by lowering vascular endothelial-cadherin levels via the activated α7 nicotinic acetylcholine receptor-mitogen activated protein kinase axis.
[So] Source:Toxicology;390:1-9, 2017 Sep 01.
[Is] ISSN:1879-3185
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Varenicline is a widely used and effective drug for smoking cessation. Despite its efficacy, varenicline increases the risk of cardiovascular disease. We previously demonstrated that varenicline aggravates atherosclerotic plaque formation in apolipoprotein E knockout mice. However, little is known about its effects in vascular endothelial cells. Therefore, we examined whether varenicline promotes migration of human umbilical vein endothelial cells (HUVECs) using the Boyden chamber assay. Varenicline (100µM) markedly promoted migration of HUVECs and decreased expression of vascular endothelial (VE)-cadherin, an endothelial adhesion molecule. Extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) signaling were markedly activated by varenicline. Methyllycaconitine (MLA; 100nM), an α7 nicotinic acetylcholine receptor (nAChR) antagonist, but not dihydro-ß-erythroidine hydrobromide (DHßE; 20µM) blocked varenicline-stimulated migration and varenicline-activated ERK, p38 and JNK signaling in HUVECs. MLA (100nM), PD98059 (an ERK inhibitor; 20µM), SB203580 (a p38 inhibitor; 20µM) and SP600125 (a JNK inhibitor; 20µM) also blocked cell migration and varenicline-induced downregulation of VE-cadherin expression in HUVECs. These findings suggest that varenicline promotes HUVEC migration by lowering VE-cadherin expression due to activated ERK/p38/JNK signaling through α7 nAChR. These processes probably contribute to varenicline-aggravated atherosclerotic plaque. Hence, an increased risk of cardiovascular events upon varenicline treatment might occur and must be considered in patients with cardiovascular diseases.
[Mh] Termos MeSH primário: Antígenos CD/metabolismo
Caderinas/metabolismo
Movimento Celular/efeitos dos fármacos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Proteínas Quinases Ativadas por Mitógeno/metabolismo
Agonistas Nicotínicos/toxicidade
Vareniclina/toxicidade
Receptor Nicotínico de Acetilcolina alfa7/agonistas
[Mh] Termos MeSH secundário: Aterosclerose/induzido quimicamente
Aterosclerose/metabolismo
Aterosclerose/patologia
Células Cultivadas
Relação Dose-Resposta a Droga
Regulação para Baixo
Agonismo Parcial de Drogas
Ativação Enzimática
Células Endoteliais da Veia Umbilical Humana/metabolismo
Células Endoteliais da Veia Umbilical Humana/patologia
Seres Humanos
Fosforilação
Medição de Risco
Transdução de Sinais/efeitos dos fármacos
Fatores de Tempo
Receptor Nicotínico de Acetilcolina alfa7/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Cadherins); 0 (Chrna7 protein, human); 0 (Nicotinic Agonists); 0 (alpha7 Nicotinic Acetylcholine Receptor); 0 (cadherin 5); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); W6HS99O8ZO (Varenicline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170827
[St] Status:MEDLINE


  10 / 2352 MEDLINE  
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[PMID]:28797116
[Au] Autor:Shelukhina I; Spirova E; Kudryavtsev D; Ojomoko L; Werner M; Methfessel C; Hollmann M; Tsetlin V
[Ad] Endereço:Department of Molecular Basis of Neurosignalling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
[Ti] Título:Calcium imaging with genetically encoded sensor Case12: Facile analysis of α7/α9 nAChR mutants.
[So] Source:PLoS One;12(8):e0181936, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Elucidation of the structural basis of pharmacological differences for highly homologous α7 and α9 nicotinic acetylcholine receptors (nAChRs) may shed light on their involvement in different physiological functions and diseases. Combination of site-directed mutagenesis and electrophysiology is a powerful tool to pinpoint the key amino-acid residues in the receptor ligand-binding site, but for α7 and α9 nAChRs it is complicated by their poor expression and fast desensitization. Here, we probed the ligand-binding properties of α7/α9 nAChR mutants by a proposed simple and fast calcium imaging method. The method is based on transient co-expression of α7/α9 nAChR mutants in neuroblastoma cells together with Ric-3 or NACHO chaperones and Case12 fluorescent calcium ion sensor followed by analysis of their pharmacology using a fluorescence microscope or a fluorometric imaging plate reader (FLIPR) with a GFP filter set. The results obtained were confirmed by electrophysiology and by calcium imaging with the conventional calcium indicator Fluo-4. The affinities for acetylcholine and epibatidine were determined for human and rat α7 nAChRs, and for their mutants with homologous residues of α9 nAChR incorporated at positions 117-119, 184, 185, 187, and 189, which are anticipated to be involved in ligand binding. The strongest decrease in the affinity was observed for mutations at positions 187 and 119. The L119D mutation of α7 nAChR, showing a larger effect for epibatidine than for acetylcholine, may implicate this position in pharmacological differences between α7 and α9 nAChRs.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Receptores Nicotínicos/genética
Receptor Nicotínico de Acetilcolina alfa7/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Seres Humanos
Mutagênese Sítio-Dirigida
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Nicotinic); 0 (alpha7 Nicotinic Acetylcholine Receptor); 0 (nAChR alpha9); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181936



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