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[PMID]:29291445
[Au] Autor:Bouhedja M; Peres B; Fhayli W; Ghandour Z; Boumendjel A; Faury G; Khelili S
[Ad] Endereço:Laboratoire de Phytochimie et de Pharmacologie, Département de Chimie, Faculté des Sciences Exactes et Informatique, Université Mohamed Seddik Ben Yahia Jijel, B.P. 98 Ouled Aissa, 18000 Jijel, Algeria; Université Grenoble-Alpes/CNRS, Département de Pharmacochimie Moléculaire UMR 5063, F-38041 Greno
[Ti] Título:Design, synthesis and biological evaluation of novel ring-opened cromakalim analogues with relaxant effects on vascular and respiratory smooth muscles and as stimulators of elastin synthesis.
[So] Source:Eur J Med Chem;144:774-796, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Two new series of ring-opened analogues of cromakalim bearing sulfonylurea moieties (series A: with N-unmethylated sulfonylureas, series B: with N-methylated sulfonylureas) were synthesized and tested as relaxants of vascular and respiratory smooth muscles (rat aorta and trachea, respectively). Ex vivo biological evaluations indicated that the most active compounds, belonging to series B, displayed a marked vasorelaxant activity on endothelium-intact aortic rings and the trachea. A majority of series B compounds exhibited a higher vasorelaxant activity (EC < 22 µM) than that of the reference compound diazoxide (EC = 24 µM). Interestingly, several tested compounds of series B also presented stronger relaxant effects on the trachea than the reference compound cromakalim (EC = 124 µM), in particular compounds B4, B7 and B16 (EC < 10 µM). By contrast, series A derivatives were poorly active on aortic rings (EC > 57 µM for all, and EC > 200 µM for a majority of them), but some of them showed an interesting relaxing effect on trachea (i.e. A15 and A33, EC = 30 µM). The most potent compounds of both series, i.e. A15, A33 and B16, tested on aortic rings in the presence of glibenclamide or 80 mM KCl, suggested that they acted as voltage-gated Ca channel blockers, like verapamil, instead of being ATP-potassium channel activators, as is cromakalim, the parent molecule. Further investigations on cultured vascular smooth muscle cells showed a strong stimulating effect on elastin synthesis, especially compound B16, which was more active at 20 µM than diazoxide, a reference ATP-sensitive potassium channel activator. Taken together, our results show that the N-methylation of the sulfonylurea moieties of ring-opened cromakalim analogues led to new compounds blocking calcium-gated channels, which had a major impact on the arterial and tracheal activities as well as selectivity.
[Mh] Termos MeSH primário: Cromakalim/farmacologia
Desenho de Drogas
Elastina/biossíntese
Músculo Liso/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Cromakalim/síntese química
Cromakalim/química
Relação Dose-Resposta a Droga
Feminino
Estrutura Molecular
Contração Muscular/efeitos dos fármacos
Ratos
Ratos Wistar
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0G4X367WA3 (Cromakalim); 9007-58-3 (Elastin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180102
[St] Status:MEDLINE


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[PMID]:28466012
[Au] Autor:Soares AG; de Carvalho MHC; Akamine E
[Ad] Endereço:Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
[Ti] Título:Obesity Induces Artery-Specific Alterations: Evaluation of Vascular Function and Inflammatory and Smooth Muscle Phenotypic Markers.
[So] Source:Biomed Res Int;2017:5038602, 2017.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vascular alterations are expected to occur in obese individuals but the impact of obesity could be different depending on the artery type. We aimed to evaluate the obesity effects on the relaxing and contractile responses and inflammatory and smooth muscle (SM) phenotypic markers in two vascular beds. Obesity was induced in C57Bl/6 mice by 16-week high-fat diet and vascular reactivity, mRNA expression of inflammatory and SM phenotypic markers, and collagen deposition were evaluated in small mesenteric arteries (SMA) and thoracic aorta (TA). Endothelium-dependent relaxation in SMA and TA was not modified by obesity. In contrast, contraction induced by depolarization and contractile agonists was reduced in SMA, whereas only contraction induced by adrenergic agonist was reduced in TA of obese mice. Obesity increased the mRNA expression of pro- and anti-inflammatory cytokines in SMA and TA. The expression of genes necessary for maintaining contractile ability was increased by obesity, but the increase was more pronounced in TA. Collagen deposition was increased in SMA, but not in TA, of obese mice. Although the endothelial function was still preserved, the SM of the two artery types was impaired by obesity, but the impairment was higher in SMA, which could be associated with SM phenotypic changes.
[Mh] Termos MeSH primário: Endotélio Vascular/metabolismo
Inflamação/genética
Músculo Liso/metabolismo
Obesidade/genética
[Mh] Termos MeSH secundário: Animais
Aorta Torácica/metabolismo
Aorta Torácica/patologia
Colágeno/metabolismo
Dieta Hiperlipídica
Modelos Animais de Doenças
Endotélio Vascular/patologia
Regulação da Expressão Gênica
Seres Humanos
Inflamação/patologia
Artérias Mesentéricas/metabolismo
Artérias Mesentéricas/patologia
Camundongos
Músculo Liso/patologia
Obesidade/patologia
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 9007-34-5 (Collagen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1155/2017/5038602


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[PMID]:29194490
[Au] Autor:Peinetti N; Scalerandi MV; Cuello Rubio MM; Leimgruber C; Nicola JP; Torres AI; Quintar AA; Maldonado CA
[Ad] Endereço:Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica. Córdoba, Argentina.
[Ti] Título:The Response of Prostate Smooth Muscle Cells to Testosterone Is Determined by the Subcellular Distribution of the Androgen Receptor.
[So] Source:Endocrinology;159(2):945-956, 2018 02 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Androgen signaling in prostate smooth muscle cells (pSMCs) is critical for the maintenance of prostate homeostasis, the alterations of which are a central aspect in the development of pathological conditions. Testosterone can act through the classic androgen receptor (AR) in the cytoplasm, eliciting genomic signaling, or through different types of receptors located at the plasma membrane for nongenomic signaling. We aimed to find evidence of nongenomic testosterone-signaling mechanisms in pSMCs and their participation in cell proliferation, differentiation, and the modulation of the response to lipopolysaccharide. We demonstrated that pSMCs can respond to testosterone by a rapid activation of ERK1/2 and Akt. Furthermore, a pool of ARs localized at the cell surface of pSMCs is responsible for a nongenomic testosterone-induced increase in cell proliferation. Through membrane receptor stimulation, testosterone favors a muscle phenotype, indicated by an increase in smooth muscle markers. We also showed that the anti-inflammatory effects of testosterone, capable of attenuating lipopolysaccharide-induced proinflammatory actions, are promoted only by receptors located inside the cell. We postulate that testosterone might perform prohomeostatic effects through intracellular-initiated mechanisms by modulating cell proliferation and inflammation, whereas some pathological, hyperproliferative actions would be induced by membrane-initiated nongenomic signaling in pSMCs.
[Mh] Termos MeSH primário: Músculo Liso/efeitos dos fármacos
Miócitos de Músculo Liso/efeitos dos fármacos
Próstata/efeitos dos fármacos
Receptores Androgênicos/metabolismo
Testosterona/farmacologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Masculino
Músculo Liso/metabolismo
Miócitos de Músculo Liso/metabolismo
Próstata/citologia
Próstata/metabolismo
Ratos Wistar
Transdução de Sinais/efeitos dos fármacos
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Receptors, Androgen); 3XMK78S47O (Testosterone)
[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:171202
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00718


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[PMID]:29216305
[Au] Autor:Gong J; Bai T; Zhang L; Qian W; Song J; Hou X
[Ad] Endereço:Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
[Ti] Título:Inhibition effect of Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis and their related products on human colonic smooth muscle in vitro.
[So] Source:PLoS One;12(12):e0189257, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To investigate the effects of four strains, generally used in clinic, including Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis, and their related products on human colonic smooth muscle in vitro. METHODS: Human colonic circular muscle strips obtained from disease-free margins of resected segments from 25 patients with colorectal cancer were isometrically examined in a constant-temperature organ bath and exposed to different concentrations of living bacteria, sonicated cell fractions and cell-free supernatant (CFS). The area under the curve (AUC) representing the contractility of smooth muscle strips was calculated. RESULTS: (1) The four living probiotics inhibited the contractility of human colonic muscle strips only at high concentration (1010 CFUs/mL, all P<0.05). (2) The sonicated cell fractions from the four probiotics obviously inhibited human colonic smooth muscle strips in a dose-dependent manner (P<0.01). (3) The CFS from the four probiotics also inhibited colonic smooth muscle strips in a dose-dependent manner (all P<0.05). (4) The inhibition effect of CFS from Streptococcus thermophilus and Enterococcus faecalis decreased obviously when pretreated with NG-nitro-L-arginine (L-NNA, 10-5 mol/L) (P<0.05), but not the Bifidobacterium longum and Lactobacillus acidophilus (P>0.05). CONCLUSION: Four common probiotics related products, including the sonicated cell fractions and the CFS, obviously inhibited human colonic smooth muscles strips contraction in a dose-dependent manner. Only high concentration living probiotics (1010 CFUs/mL) can inhibit the colonic smooth muscles strips contraction. The NO pathway may be partly involved in the inhibitory effect of CFS from Streptococcus thermophilus and Enterococcus faecalis.
[Mh] Termos MeSH primário: Bifidobacterium longum
Colo/fisiologia
Enterococcus faecalis
Lactobacillus acidophilus
Músculo Liso/fisiologia
Probióticos
Streptococcus thermophilus
[Mh] Termos MeSH secundário: Neoplasias do Colo/fisiopatologia
Neoplasias do Colo/cirurgia
Seres Humanos
Contração Muscular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189257


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[PMID]:28743514
[Au] Autor:Herbert J; Thiermann H; Worek F; Wille T
[Ad] Endereço:Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
[Ti] Título:Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning.
[So] Source:Toxicology;389:94-100, 2017 08 15.
[Is] ISSN:1879-3185
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Standard therapeutic options in organophosphate (OP) poisoning are limited to the administration of atropine and oximes, a regimen often lacking in efficacy and applicability. Treatment alternatives are needed, preferably covering a broad spectrum of OP intoxications. Although recent research yielded several promising compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) receptor or bispyridinium non-oximes, these substances still need further evaluation, especially regarding effects on the potentially lethal respiratory symptoms of OP poisoning. Aim of this study was the development of an applicable and easy method to test the therapeutic efficiency of such substances. For this purpose, airway responsiveness in viable precision cut lung slices (PCLS) from rats was analysed. We showed that ACh-induced airway contractions were spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS, contractions were irreversible. This effect could be antagonized by addition of the standard therapeutic atropine, thereby presenting a clear indication for treatment efficiency. Now, candidate therapeutic compounds can be evaluated, based on their ability to counteract the irreversible airway contraction in OP poisoned PCLS.
[Mh] Termos MeSH primário: Antídotos/farmacologia
Atropina/farmacologia
Broncoconstrição/efeitos dos fármacos
Broncodilatadores/farmacologia
Descoberta de Drogas/métodos
Pulmão/efeitos dos fármacos
Antagonistas Muscarínicos/farmacologia
Contração Muscular/efeitos dos fármacos
Músculo Liso/efeitos dos fármacos
Agentes Neurotóxicos/toxicidade
Intoxicação por Organofosfatos/tratamento farmacológico
Organofosfatos/toxicidade
[Mh] Termos MeSH secundário: Acetilcolina/farmacologia
Animais
Relação Dose-Resposta a Droga
Pulmão/fisiopatologia
Masculino
Músculo Liso/fisiopatologia
Intoxicação por Organofosfatos/fisiopatologia
Ratos Wistar
Fatores de Tempo
Técnicas de Cultura de Tecidos
Sobrevivência de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antidotes); 0 (Bronchodilator Agents); 0 (Muscarinic Antagonists); 0 (Nerve Agents); 0 (Organophosphates); 7C0697DR9I (Atropine); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE


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[PMID]:29283233
[Au] Autor:Tsirkin VI; Nozdrachev AD; Sizova EN; Polezhaeva TV; Khlybova SV
[Ti] Título:Endogenous Sensitizer of Beta-Adrenergic Receptors (ESBAR) as a Component of Humoral Links Element of Autonomic Nervous System and Its Analogs (Review).
[So] Source:Usp Fiziol Nauk;47(4):18-42, 2016 Oct-Dec.
[Is] ISSN:0301-1798
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Kirov State Medical Academy, Kirov The results of the 20-years studies of the presence in blood serum and other body fluids of endogenous modulators of adrenergic and M-cholinergic impact a A COMPONENT of humoral element of autonomic nervous system. The article is devoted to the endogenous sensitizer of beta-adrenergic receptor (ESBAR) - water-soluble low molecular weight substances, analogues of which are histidine, tryptophan, tyrosine, mildronat and preduktal. It is shown, that separate dilutions of human serum and animal (as a source of ESBAR) and ESBAR - analogues ways to enhance the effectiveness of activation of beta-adrenoceptors (AR) of smooth muscle (uterus, coronary and renal arteries, trachea, stomach), myocardium and erythrocytes and platelets (respectively influenced of histidine and tryptophan). It is reported? that content of ESBAR in human serum (according to the titers of its dilution) depends on the sex and the presence of somatic diseases, and at women are also on the stage of reproduction and obstetric complications It is discussed hossible mechanisms of ESBAR action, its physiological role, including as a component of beta-adrenoreceptor myometrium inhibitory mechanism, as well as the prospect of the use of analogues ESBAR, including for the prevention of preterm labor, and for the treatment of bronchial asthma, coronary heart disease, hypertension and heart failure.
[Mh] Termos MeSH primário: Agonistas Adrenérgicos/uso terapêutico
Sistema Nervoso Autônomo/efeitos dos fármacos
Agonistas Colinérgicos/uso terapêutico
Insuficiência Cardíaca/prevenção & controle
Músculo Liso/efeitos dos fármacos
Trabalho de Parto Prematuro/prevenção & controle
[Mh] Termos MeSH secundário: Agonistas Adrenérgicos/sangue
Asma/tratamento farmacológico
Asma/metabolismo
Asma/fisiopatologia
Sistema Nervoso Autônomo/metabolismo
Sistema Nervoso Autônomo/fisiopatologia
Agonistas Colinérgicos/sangue
Doença das Coronárias/tratamento farmacológico
Doença das Coronárias/metabolismo
Doença das Coronárias/fisiopatologia
Feminino
Insuficiência Cardíaca/metabolismo
Insuficiência Cardíaca/fisiopatologia
Histidina/sangue
Histidina/uso terapêutico
Seres Humanos
Hipertensão/tratamento farmacológico
Hipertensão/metabolismo
Hipertensão/fisiopatologia
Metilidrazinas/uso terapêutico
Músculo Liso/metabolismo
Músculo Liso/fisiopatologia
Trabalho de Parto Prematuro/metabolismo
Trabalho de Parto Prematuro/fisiopatologia
Gravidez
Triptofano/sangue
Triptofano/uso terapêutico
Tirosina/sangue
Tirosina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adrenergic Agonists); 0 (Cholinergic Agonists); 0 (Methylhydrazines); 42HK56048U (Tyrosine); 4QD397987E (Histidine); 73H7UDN6EC (3-(2,2,2-trimethylhydrazine)propionate); 8DUH1N11BX (Tryptophan)
[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:171229
[St] Status:MEDLINE


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[PMID]:29267380
[Au] Autor:Kuga N; Tanioka A; Hagihara K; Kawai T
[Ad] Endereço:Pharmacology Research Laboratory, Watarase Research Center, Kyorin Pharmaceutical Company, Limited, Nogi, Tochigi, Japan.
[Ti] Título:Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states.
[So] Source:PLoS One;12(12):e0189941, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases.
[Mh] Termos MeSH primário: Vias Aferentes/efeitos dos fármacos
Músculo Liso/efeitos dos fármacos
Bexiga Urinária/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Ciclofosfamida/farmacologia
Feminino
Contração Muscular/efeitos dos fármacos
Músculo Liso/patologia
Ratos
Ratos Sprague-Dawley
Bexiga Urinária/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
8N3DW7272P (Cyclophosphamide)
[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:171222
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189941


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[PMID]:29236387
[Au] Autor:Virych PA; Shelyuk OV; Kabanova TA; Khalimova EI; Martynyuk VS; Pavlovsky VI; Andronati SA
[Ti] Título:Effect of 3-substituted 1,4-benzodiazepin-2-ones on bradykinin-induced smooth muscle contraction.
[So] Source:Ukr Biochem J;89(1):31-7, 2017 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:Biochemical properties of 3-substituted 1,4-benzodiazepine determined by the characteristics of their chemical structure. Influence of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate and amplitudes of isometric smooth muscle contraction in rats was investigated. Compounds MX-1775 and MX-1828 demonstrated the similar inhibition effect on bradykinin-induced contraction of smooth muscle like competitive inhibitor des-arg9-bradykinin-acetate to bradykinin B2-receptors. MX-1626 demonstrated unidirectional changes of maximal normalized rate and force of smooth muscle that proportionally depended on bradykinin concentration in the range 10-10-10-6 M. MX-1828 has statistically significant decrease of normalized rate of smooth muscle contraction for bradykinin concentrations 10-10 and 10-9 M by 20.7 and 8.6%, respectively, but for agonist concentration 10-6 M, this parameter increased by 10.7% and amplitude was reduced by 29.5%. Compounds MX-2011, MX-1785 and MX-2004 showed no natural effect on bradykinin-induced smooth muscle contraction. Compounds MX-1775, MX-1828, MX-1626 were selected for further research of their influence on kinin-kallikrein system and pain perception.
[Mh] Termos MeSH primário: Benzodiazepinas/farmacologia
Bradicinina/farmacologia
Contração Isométrica/efeitos dos fármacos
Músculo Liso/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Benzodiazepinas/síntese química
Benzodiazepinas/química
Bradicinina/análogos & derivados
Bradicinina/metabolismo
Relação Dose-Resposta a Droga
Contração Isométrica/fisiologia
Masculino
Músculo Liso/fisiologia
Ratos
Receptor B2 da Bradicinina/metabolismo
Estômago/efeitos dos fármacos
Estômago/fisiologia
Relação Estrutura-Atividade
Técnicas de Cultura de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptor, Bradykinin B2); 12794-10-4 (Benzodiazepines); S8TIM42R2W (Bradykinin)
[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:171214
[St] Status:MEDLINE
[do] DOI:10.15407/ubj89.01.031


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[PMID]:29235753
[Ti] Título:The influence of heavy metal ions, spermine and sodium nitroprusside on ATP-hydrolases of cell membranes of rat colon smooth muscle.
[So] Source:Ukr Biochem J;88(4):20-8, 2016 Jul-Aug.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:The specific features of functional lability of the rat colon smooth muscle (CSM) АТР-hydrolases were studied. Na+,K+-AТРase activity is effectively inhibited by divalent ions of both transition (≥ 0,1 µM) and nontransition (≥ 1 µM) heavy metals in succession by efficiency: Cu2+ > Fe2+ ≥ Cd2+ (10 µM). Polyamine spermine (0,5-1,0 mM) is a weak Na+,K+-AТРase inhibitor at saturation concentrations of ions and substrate. Sodium nitroprusside (1 mM) as nitric oxide-generating compound exhibits weak Na+,K+-AТРase inhibition only after prolonged preincubation with membranes. Mg2+-АТР-hydrolase activity in all cases is much more resistant to studied agents. Considering the example of the CSM Na+,K+-AТРase it is assumed that enzyme has specific biochemical features that contribute to its role as a potential target and redox-sensor, mediating the pathological mechanisms of heavy metal intoxication and cell oxidative damage.
[Mh] Termos MeSH primário: Adenosina Trifosfatases/metabolismo
Membrana Celular/efeitos dos fármacos
Metais Pesados/farmacologia
Nitroprussiato/farmacologia
ATPase Trocadora de Sódio-Potássio/metabolismo
Espermina/farmacologia
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/antagonistas & inibidores
Animais
Cádmio/farmacologia
Cátions Bivalentes
Fracionamento Celular
Membrana Celular/metabolismo
Colo/citologia
Colo/enzimologia
Cobre/farmacologia
Ferro/farmacologia
Cinética
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Músculo Liso/citologia
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Miócitos de Músculo Liso/citologia
Miócitos de Músculo Liso/enzimologia
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Ratos Wistar
ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cations, Divalent); 0 (Metals, Heavy); 00BH33GNGH (Cadmium); 169D1260KM (Nitroprusside); 2FZ7Y3VOQX (Spermine); 789U1901C5 (Copper); E1UOL152H7 (Iron); EC 3.6.1.- (Adenosine Triphosphatases); EC 3.6.1.- (magnesium sodium ATPase); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase)
[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:171214
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.04.020


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[PMID]:29196050
[Au] Autor:Kothencz A; Hajagos-Tóth J; Csányi A; Gáspár R
[Ad] Endereço:Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary.
[Ti] Título:Alpha-tocopherol succinate increases cyclooxygenase-2 activity: Tissue-specific action in pregnant rat uterus in vitro.
[So] Source:Life Sci;192:199-204, 2018 Jan 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Lipid soluble vitamin E plays a role in several physiological mechanisms, however, the mechanism of this action is controversial. We investigated how tocopherol (α-tocopherol acid succinate) influences the effects of cyclooxygenase inhibitors (COXi) in the smooth muscles. MAIN METHODS: The contractility of the samples from 22-day-pregnant myometrium and non-pregnant myometrium and trachea was determined in an isolated organ bath in vitro. The activity of cyclooxygenase enzymes (COX) was also measured in the tissues. KEY FINDINGS: Diclofenac (10 -10 M) and rofecoxib (10 -10 M) decreased the contractions in non-pregnant and 22-day-pregnant uteri. Tocopherol (10 M) increased the relaxant effect only in pregnant uteri. Both diclofenac (10 -10 M) and rofecoxib (10 -10 M) reduced the tracheal tones, while they were slightly intensified by pretreatment with tocopherol (10 M). Tocopherol enhanced the contractions of pregnant uteri. Tocopherol (10 M) itself can induce the cyclooxygenase activity and shift the COX-1 and COX-2 ratio to COX-2. The lowest COX activity was found in non-pregnant uteri, while the highest one was in the trachea. SIGNIFICANCE: The COX enzymes, especially COX-2, play an important role in the contraction of pregnant uteri in rat. Tocopherol has a tissue specific COX-2 activity increasing effect in pregnant rat uterus but has no such action in non-pregnant uteri or tracheal tissue. Hereby, tocopherol may intensify selectively the uterine relaxing effect of COX-2 inhibitors in preterm contractions. However, tocopherol can enhance the contractile response of pregnant uterus that may increase the risk of premature contractions.
[Mh] Termos MeSH primário: Ciclo-Oxigenase 2/biossíntese
Útero/enzimologia
alfa-Tocoferol/farmacologia
[Mh] Termos MeSH secundário: Animais
Ciclo-Oxigenase 1/metabolismo
Inibidores de Ciclo-Oxigenase 2/farmacologia
Feminino
Técnicas In Vitro
Proteínas de Membrana/metabolismo
Músculo Liso/efeitos dos fármacos
Miométrio/efeitos dos fármacos
Miométrio/enzimologia
Miométrio/metabolismo
Especificidade de Órgãos
Gravidez
Ratos
Ratos Sprague-Dawley
Traqueia/enzimologia
Contração Uterina/efeitos dos fármacos
Útero/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclooxygenase 2 Inhibitors); 0 (Membrane Proteins); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (Ptgs1 protein, rat); EC 1.14.99.1 (Ptgs2 protein, rat); H4N855PNZ1 (alpha-Tocopherol)
[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:171203
[St] Status:MEDLINE



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