Base de dados : MEDLINE
Pesquisa : D12.776.543.750.695.475.200 [Categoria DeCS]
Referências encontradas : 1382 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 139 ir para página                         

  1 / 1382 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28461224
[Au] Autor:Li X; Obeidat M; Zhou G; Leung JM; Tashkin D; Wise R; Connett J; Joubert P; Bossé Y; van den Berge M; Brandsma CA; Nickle DC; Hao K; Paré PD; Sin DD
[Ad] Endereço:UBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.
[Ti] Título:Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease.
[So] Source:EBioMedicine;19:139-145, 2017 May.
[Is] ISSN:2352-3964
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients. Here, we determined whether there is any significant sex-related differences in FEV responses to ipratropium bromide. METHODS: Data from the Lung Health Study (n=5887; 37% females) were used to determine changes in FEV with ipratropium or placebo in male and female subjects with mild to moderate COPD over 5years. Lung Expression Quantitative Trait Loci (eQTL) dataset was used to determine whether there were any sex-related differences in gene expression for muscarinic (M2 and M3) receptors in lungs of male and female patients. RESULTS: After 4months, ipratropium therapy increased FEV by 6.0% in female and 2.9% in male subjects from baseline values (p=2.42×10 ). This effect was modified by body mass index (BMI) such that the biggest improvements in FEV with ipratropium were observed in thin female subjects (p for BMI∗sex interaction=0.044). The sex-related changes in FEV related to ipratropium persisted for 2years (p=0.0134). Female compared with male lungs had greater gene expression for M3 relative to M2 receptors (p=6.86×10 ). CONCLUSION: Ipratropium induces a larger bronchodilator response in female than in male patients and the benefits are particularly notable in non-obese females. Female lungs have greater gene expression for the M3 muscarinic receptor relative to M2 receptors than male lungs. Female patients are thus more likely to benefit from ipratropium than male COPD patients.
[Mh] Termos MeSH primário: Broncodilatadores/uso terapêutico
Antagonistas Colinérgicos/uso terapêutico
Ipratrópio/uso terapêutico
Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Índice de Massa Corporal
Feminino
Volume Expiratório Forçado
Expressão Gênica
Seres Humanos
Masculino
Meia-Idade
Doença Pulmonar Obstrutiva Crônica/genética
Doença Pulmonar Obstrutiva Crônica/fisiopatologia
Receptor Muscarínico M2/genética
Receptor Muscarínico M3/genética
Caracteres Sexuais
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Bronchodilator Agents); 0 (Cholinergic Antagonists); 0 (Receptor, Muscarinic M2); 0 (Receptor, Muscarinic M3); GR88G0I6UL (Ipratropium)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  2 / 1382 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29305262
[Au] Autor:Ågren R; Sahlholm K; Nilsson J; Århem P
[Ad] Endereço:Department of Neuroscience, Retzius väg 8, Karolinska Institutet, SE-171 77, Stockholm, Sweden. Electronic address: richard.agren@stud.ki.se.
[Ti] Título:Point mutation of a conserved aspartate, D69, in the muscarinic M receptor does not modify voltage-sensitive agonist potency.
[So] Source:Biochem Biophys Res Commun;496(1):101-104, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The muscarinic M receptor (M R) has been shown to display voltage-sensitive agonist binding, based on G protein-activated inward rectifier potassium channel (GIRK) opening and radioligand binding at different membrane voltages. A conserved aspartate in transmembrane segment (TM) II of M R, D69, has been proposed as the voltage sensor. While a recent paper instead presented evidence of tyrosines in TMs III, VI, and VII acting as voltage sensors, these authors were not able to record GIRK channel activation by a D69N mutant M R. In the present study, we succeeded in recording ACh-induced GIRK channel activation by this mutant at -80 and 0 mV. The acetylcholine EC was about 2.5-fold higher at 0 mV, a potency shift very similar to that observed at wild-type M R, indicating that voltage sensitivity persists at the D69N mutant. Thus, our present observations corroborate the notion that D69 is not responsible for voltage sensitivity of the M R.
[Mh] Termos MeSH primário: Acetilcolina/administração & dosagem
Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/metabolismo
Potenciais da Membrana/efeitos dos fármacos
Potenciais da Membrana/fisiologia
Receptor Muscarínico M2/genética
Receptor Muscarínico M2/metabolismo
[Mh] Termos MeSH secundário: Animais
Ácido Aspártico/genética
Células Cultivadas
Sequência Conservada
Relação Dose-Resposta a Droga
Mutagênese Sítio-Dirigida
Oócitos
Mutação Puntual/genética
Receptor Muscarínico M2/efeitos dos fármacos
Relação Estrutura-Atividade
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels); 0 (Receptor, Muscarinic M2); 30KYC7MIAI (Aspartic Acid); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


  3 / 1382 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28463115
[Au] Autor:O'Hern PJ; do Carmo G Gonçalves I; Brecht J; López Soto EJ; Simon J; Chapkis N; Lipscombe D; Kye MJ; Hart AC
[Ad] Endereço:Department of Neuroscience, Brown University, Providence, United States.
[Ti] Título:Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models.
[So] Source:Elife;6, 2017 05 02.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Spinal Muscular Atrophy (SMA) is caused by diminished Survival of Motor Neuron (SMN) protein, leading to neuromuscular junction (NMJ) dysfunction and spinal motor neuron (MN) loss. Here, we report that reduced SMN function impacts the action of a pertinent microRNA and its mRNA target in MNs. Loss of the SMN ortholog, SMN-1, causes NMJ defects. We found that increased levels of the Gemin3 ortholog, MEL-46, ameliorates these defects. Increased MEL-46 levels also restored perturbed microRNA (miR-2) function in animals. We determined that miR-2 regulates expression of the M2 muscarinic receptor (m2R) ortholog, GAR-2. GAR-2 loss ameliorated and synaptic defects. In an SMA mouse model, m2R levels were increased and pharmacological inhibition of m2R rescued MN process defects. Collectively, these results suggest decreased SMN leads to defective microRNA function MEL-46 misregulation, followed by increased m2R expression, and neuronal dysfunction in SMA.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/metabolismo
Caenorhabditis elegans
MicroRNAs/metabolismo
Atrofia Muscular Espinal/fisiopatologia
Receptor Muscarínico M2/análise
Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo
[Mh] Termos MeSH secundário: Animais
RNA Helicases DEAD-box/metabolismo
Modelos Animais de Doenças
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (MEL-46 protein, C elegans); 0 (MicroRNAs); 0 (Receptor, Muscarinic M2); 0 (SMN1 protein, C elegans); 0 (Survival of Motor Neuron 1 Protein); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180211
[Lr] Data última revisão:
180211
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  4 / 1382 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28722769
[Au] Autor:Sakata K; Overacre AE
[Ad] Endereço:Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, USA.
[Ti] Título:Promoter IV-BDNF deficiency disturbs cholinergic gene expression of CHRNA5, CHRM2, and CHRM5: effects of drug and environmental treatments.
[So] Source:J Neurochem;143(1):49-64, 2017 Oct.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Brain-derived neurotrophic factor (BDNF) promotes maturation of cholinergic neurons. However, how activity-dependent BDNF expression affects specific cholinergic gene expression remains unclear. This study addressed this question by determining mRNA levels of 22 acetylcholine receptor subunits, the choline transporter (CHT), and the choline acetyltransferase (ChAT) in mice deficient in activity-dependent BDNF via promoter IV (KIV) and control wild-type mice. Quantitative RT-PCR revealed significant reductions in nicotinic acetylcholine receptor alpha 5 (CHRNA5) in the frontal cortex and hippocampus and M5 muscarinic acetylcholine receptor (CHRM5) in the hippocampus, but significant increases in M2 muscarinic acetylcholine receptor (CHRM2) in the frontal cortex of KIV mice compared to wild-type mice. Three-week treatments with fluoxetine, phenelzine, duloxetine, imipramine, or an enriched environment treatment (EET) did not affect the altered expression of these genes except that EET increased CHRNA5 levels only in KIV frontal cortex. EET also increased levels of CHRNA7, CHT, and ChAT, again only in the KIV frontal cortex. The imipramine treatment was most prominent among the four antidepressants; it up-regulated hippocampal CHRM2 and frontal cortex CHRM5 in both genotypes, and frontal cortex CHRNA7 only in KIV mice. To the best of our knowledge, this is the first evidence that BDNF deficiency disturbs expression of CHRNA5, CHRM2, and CHRM5. Our results suggest that promoter IV-BDNF deficiency - which occurs under chronic stress - causes cholinergic dysfunctions via these receptors. EET is effective on CHRNA5, while its compensatory induction of other cholinergic genes or drugs targeting CHRNA5, CHRM2, and CHRM5 may become an alternative strategy to reverse these BDNF-linked cholinergic dysfunctions.
[Mh] Termos MeSH primário: Antidepressivos/farmacologia
Fator Neurotrófico Derivado do Encéfalo/deficiência
Meio Ambiente
Receptor Muscarínico M2/biossíntese
Receptor Muscarínico M5/biossíntese
Receptores Nicotínicos/biossíntese
[Mh] Termos MeSH secundário: Animais
Fator Neurotrófico Derivado do Encéfalo/genética
Feminino
Lobo Frontal/efeitos dos fármacos
Lobo Frontal/metabolismo
Expressão Gênica
Hipocampo/efeitos dos fármacos
Hipocampo/metabolismo
Masculino
Camundongos
Camundongos da Linhagem 129
Camundongos Endogâmicos C57BL
Regiões Promotoras Genéticas/efeitos dos fármacos
Regiões Promotoras Genéticas/fisiologia
Receptor Muscarínico M2/genética
Receptor Muscarínico M5/genética
Receptores Nicotínicos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Brain-Derived Neurotrophic Factor); 0 (CHRM2 protein, human); 0 (CHRNA5 protein, mouse); 0 (Receptor, Muscarinic M2); 0 (Receptor, Muscarinic M5); 0 (Receptors, Nicotinic)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.14129


  5 / 1382 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28388054
[Au] Autor:Pegoli A; She X; Wifling D; Hübner H; Bernhardt G; Gmeiner P; Keller M
[Ad] Endereço:Institute of Pharmacy, Faculty of Chemistry and Pharmacy, University of Regensburg , Universitätsstrasse 31, D-93053 Regensburg, Germany.
[Ti] Título:Radiolabeled Dibenzodiazepinone-Type Antagonists Give Evidence of Dualsteric Binding at the M Muscarinic Acetylcholine Receptor.
[So] Source:J Med Chem;60(8):3314-3334, 2017 Apr 27.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The dualsteric ligand approach, aiming at ligands with improved subtype selectivity, has been increasingly applied to muscarinic receptors (MRs). In this article, we present the synthesis and characterization of a M R subtype-preferring radiolabeled dibenzodiazepinone-type antagonist ([ H]UNSW-MK259, [ H]19) and its homodimeric analogue [ H]UR-AP060 ([ H]33). Saturation binding studies at the M R, using the orthosteric antagonist atropine to determine unspecific binding, proved that the monomeric and the dimeric compound bind to the orthosteric binding site (apparent K : 0.87 and 0.31 nM, respectively). Various binding studies with [ H]19 and [ H]33 at the M R, for instance, saturation binding experiments in the presence of the allosteric MR modulators W84 (8) or LY2119620 (9) (Schild-like analysis) suggested a competitive mechanism between the allosteric modulator and the dibenzodiazepinone derivatives, and thus a dualsteric binding mode of both 19 and 33. This was consistent with the results of M R MD simulations (≥2 µs) performed with 19 and 33.
[Mh] Termos MeSH primário: Benzodiazepinonas/metabolismo
Antagonistas Muscarínicos/farmacologia
Radioisótopos/química
Receptor Muscarínico M2/antagonistas & inibidores
[Mh] Termos MeSH secundário: Sítios de Ligação
Simulação de Dinâmica Molecular
Receptor Muscarínico M2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzodiazepinones); 0 (Muscarinic Antagonists); 0 (Radioisotopes); 0 (Receptor, Muscarinic M2)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170620
[Lr] Data última revisão:
170620
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.6b01892


  6 / 1382 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28212895
[Au] Autor:Slupecka M; Grzesiak P; Kwiatkowski J; Gajewska M; Kuwahara A; Kato I; Wolinski J
[Ad] Endereço:Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Jablonna, Poland. Electronic address: m.slupecka@ifzz.pl.
[Ti] Título:The influence of enteral obestatin administration to suckling rats on intestinal contractility.
[So] Source:Gen Comp Endocrinol;248:69-78, 2017 Jul 01.
[Is] ISSN:1095-6840
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study investigated the effect of enteral administration of obestatin on the contractility of whole-thickness preparations of duodenum and middle jejunum, as well as on the morphology of the enteric nervous system (ENS). Suckling rats were assigned to 3 groups (n=12) treated with: C-saline solution; LO-obestatin (125nmol/kgb.wt); HO-obestatin (250nmol/kgb.wt). Saline solution or obestatin were administered twice daily, from the 14th to the 21st day of life. Sections were studied in an organ bath, for isometric recording in the presence of acetylocholine (ACh), atropine (ATR) and tetradotoxin (TTX). Thickness of intestinal muscularis layer, the number of interstitial cells of Cajal (ICC) were measured in the paraffin sections. The immunodetection of Muscarinic Acetylocholine Receptor 2 (M2 receptor) was performed in the intestinal segments. In both intestinal segments HO treatment decreased the amplitude of spontaneous contraction compared to that observed in the C group. In the middle jejunum, the LO treatment also decreased the amplitude. TTX and ATR had no effect on amplitude of spontaneous contraction in the jejunum of LO and HO-treated animals. Compared to the C group, duodenal sections from HO animals and middle jejunum sections from LO and HO groups displayed a lower amplitude in response to ACh and EFS evoked contraction. An increase in the thickness of the muscularis layer was observed in the duodenum of LO and HO groups whereas the number ICC did not change significantly after treatment with obestatin. Moreover, the enteral administration of obestatin did not effect significantly on the cytoplasmic expression of M2 receptor in the jejunum. Our study demonstrated that enteral administration of obestatin to suckling rats influences small intestine contractility in the segment specific manner.
[Mh] Termos MeSH primário: Motilidade Gastrointestinal/fisiologia
Grelina/administração & dosagem
Grelina/farmacologia
Intestinos/fisiologia
Contração Muscular/efeitos dos fármacos
[Mh] Termos MeSH secundário: Acetilcolina/farmacologia
Animais
Contagem de Células
Estimulação Elétrica
Nutrição Enteral
Feminino
Motilidade Gastrointestinal/efeitos dos fármacos
Células Intersticiais de Cajal/citologia
Células Intersticiais de Cajal/efeitos dos fármacos
Intestinos/efeitos dos fármacos
Masculino
Proteínas Proto-Oncogênicas c-kit/metabolismo
Ratos
Receptor Muscarínico M2
Tetrodotoxina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ghrelin); 0 (Receptor, Muscarinic M2); 4368-28-9 (Tetrodotoxin); EC 2.7.10.1 (Proto-Oncogene Proteins c-kit); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170219
[St] Status:MEDLINE


  7 / 1382 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28167741
[Au] Autor:De Min A; Matera C; Bock A; Holze J; Kloeckner J; Muth M; Traenkle C; De Amici M; Kenakin T; Holzgrabe U; Dallanoce C; Kostenis E; Mohr K; Schrage R
[Ad] Endereço:Pharmacology and Toxicology Section, Institute of Pharmacy (A.D.M., J.H., C.T., K.M., R.S.), Research Training Group 1873 (A.D.M., E.K., K.M.), and Molecular-, Cellular-, and Pharmacobiology Section, Institute of Pharmaceutical Biology (E.K.), University of Bonn, Bonn, Germany; Dipartimento di Scien
[Ti] Título:A New Molecular Mechanism To Engineer Protean Agonism at a G Protein-Coupled Receptor.
[So] Source:Mol Pharmacol;91(4):348-356, 2017 Apr.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protean agonists are of great pharmacological interest as their behavior may change in magnitude and direction depending on the constitutive activity of a receptor. Yet, this intriguing phenomenon has been poorly described and understood, due to the lack of stable experimental systems and design strategies. In this study, we overcome both limitations: First, we demonstrate that modulation of the ionic strength in a defined experimental set-up allows for analysis of G protein-coupled receptor activation in the absence and presence of a specific amount of spontaneous receptor activity using the muscarinic M acetylcholine receptor as a model. Second, we employ this assay system to show that a dualsteric design principle, that is, molecular probes, carrying two pharmacophores to simultaneously adopt orthosteric and allosteric topography within a G protein-coupled receptor, may represent a novel approach to achieve protean agonism. We pinpoint three molecular requirements within dualsteric compounds that elicit protean agonism at the muscarinic M acetylcholine receptor. Using radioligand-binding and functional assays, we posit that dynamic ligand binding may be the mechanism underlying protean agonism of dualsteric ligands. Our findings provide both new mechanistic insights into the still enigmatic phenomenon of protean agonism and a rationale for the design of such compounds for a G protein-coupled receptor.
[Mh] Termos MeSH primário: Engenharia de Proteínas
Receptores Acoplados a Proteínas-G/agonistas
[Mh] Termos MeSH secundário: Regulação Alostérica
Animais
Células CHO
Cricetinae
Cricetulus
Seres Humanos
Ligantes
Ligação Proteica
Receptor Muscarínico M2/metabolismo
Receptores Acoplados a Proteínas-G/metabolismo
Trometamina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Receptor, Muscarinic M2); 0 (Receptors, G-Protein-Coupled); 023C2WHX2V (Tromethamine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170208
[St] Status:MEDLINE
[do] DOI:10.1124/mol.116.107276


  8 / 1382 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28122499
[Au] Autor:Kim JE; Go J; Sung JE; Lee HA; Yun WB; Hong JT; Hwang DY
[Ad] Endereço:Department of Biomaterials Science, College of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, 50 Cheonghak-ri, Samnangjin-eup Miryang-si, Gyeongsangnam-do, 627-706, Korea.
[Ti] Título:Uridine stimulate laxative effect in the loperamide-induced constipation of SD rats through regulation of the mAChRs signaling pathway and mucin secretion.
[So] Source:BMC Gastroenterol;17(1):21, 2017 Jan 26.
[Is] ISSN:1471-230X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Uridine (Urd), which has been reported as a major component of RNA, plays an important role in various biological process including neuroprotection, biochemical modulation and glycolysis, although its role in constipation has yet to be established. Therefore, in this study, we investigated the laxative effects of Urd on chronic constipation. METHODS: The constipation phenotypes and their related mechanisms were investigated in the transverse colons of SD rats with loperamide (Lop)-induced constipation after treatment with 100 mg/kg of Urd. RESULTS: The number, weight and water contents of stools were significantly higher in the Lop + Urd treated group than the Lop + Vehicle treated group, while food intake and water consumption of the same group were maintained at a constant level. The thickness of the mucosa layer, muscle and flat luminal surface, as well as the number of goblet cells, paneth cells and lipid droplets were enhanced in the Lop + Urd treated group. Furthermore, the expression of the muscarinic acetylcholine receptors M2 and M3 (mAChR M2 and M3) at the transcriptional and translational level was recovered in the Lop + Urd treated group, while some markers such as Gα and inositol triphosphate (IP3) in their downstream signaling pathway were completely recovered by Urd treatment. Moreover, the ability for mucin secretion and the expression of membrane water channel (aquaporine 8, AQP8) were increased significantly in the Lop + Urd treated group compared with Lop + Vehicle treated group. Finally, the activity of Urd was confirmed in primary smooth muscle of rat intestine cells (pRISMC) based on Gα expression and IP3 concentration. CONCLUSIONS: The results of the present study provide the first strong evidence that Urd can be considered an important candidate for improving chronic constipation induced by Lop treatment in animal models.
[Mh] Termos MeSH primário: Constipação Intestinal/tratamento farmacológico
Constipação Intestinal/metabolismo
Laxantes/uso terapêutico
Mucinas/secreção
Receptor Muscarínico M2/metabolismo
Receptor Muscarínico M3/metabolismo
Uridina/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Colo Transverso/efeitos dos fármacos
Colo Transverso/patologia
Colo Transverso/ultraestrutura
Modelos Animais de Doenças
Comportamento Alimentar/efeitos dos fármacos
Fosfatos de Inositol/metabolismo
Intestinos/metabolismo
Mucinas/efeitos dos fármacos
Músculo Liso/metabolismo
Ratos Sprague-Dawley
Receptor Muscarínico M2/efeitos dos fármacos
Receptor Muscarínico M3/efeitos dos fármacos
Transdução de Sinais
Uridina/metabolismo
Uridina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Inositol Phosphates); 0 (Laxatives); 0 (Mucins); 0 (Receptor, Muscarinic M2); 0 (Receptor, Muscarinic M3); 0 (inositol trispyrophosphate); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170127
[St] Status:MEDLINE
[do] DOI:10.1186/s12876-017-0576-y


  9 / 1382 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28082514
[Au] Autor:Seemann WK; Wenzel D; Schrage R; Etscheid J; Bödefeld T; Bartol A; Warnken M; Sasse P; Klöckner J; Holzgrabe U; DeAmici M; Schlicker E; Racké K; Kostenis E; Meyer R; Fleischmann BK; Mohr K
[Ad] Endereço:Pharmacology and Toxicology Section, Institute of Pharmacy, University of Bonn, Bonn, Germany (W.K.S., R.S., J.E., T.B., A.B., K.M.); Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Bonn, Germany (D.W., P.S., B.K.F.); Institute of Pharmacology & Toxicology,
[Ti] Título:Engineered Context-Sensitive Agonism: Tissue-Selective Drug Signaling through a G Protein-Coupled Receptor.
[So] Source:J Pharmacol Exp Ther;360(2):289-299, 2017 Feb.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Drug discovery strives for selective ligands to achieve targeted modulation of tissue function. Here we introduce engineered context-sensitive agonism as a postreceptor mechanism for tissue-selective drug action through a G protein-coupled receptor. Acetylcholine M -receptor activation is known to mediate, among other actions, potentially dangerous slowing of the heart rate. This unwanted side effect is one of the main reasons that limit clinical application of muscarinic agonists. Herein we show that dualsteric (orthosteric/allosteric) agonists induce less cardiac depression ex vivo and in vivo than conventional full agonists. Exploration of the underlying mechanism in living cells employing cellular dynamic mass redistribution identified context-sensitive agonism of these dualsteric agonists. They translate elevation of intracellular cAMP into a switch from full to partial agonism. Designed context-sensitive agonism opens an avenue toward postreceptor pharmacologic selectivity, which even works in target tissues operated by the same subtype of pharmacologic receptor.
[Mh] Termos MeSH primário: Descoberta de Drogas
Agonistas Muscarínicos/farmacologia
Receptor Muscarínico M2/agonistas
Receptor Muscarínico M2/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica/efeitos dos fármacos
Animais
Células CHO
Cricetinae
Cricetulus
AMP Cíclico/metabolismo
Feminino
Coração/efeitos dos fármacos
Espaço Intracelular/efeitos dos fármacos
Espaço Intracelular/metabolismo
Masculino
Camundongos
Agonistas Muscarínicos/efeitos adversos
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Muscarinic Agonists); 0 (Receptor, Muscarinic M2); E0399OZS9N (Cyclic AMP)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170516
[Lr] Data última revisão:
170516
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170114
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.116.237149


  10 / 1382 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28012380
[Au] Autor:Zhou M; Ma X; Ding G; Wang Z; Liu D; Tong Y; Zhou H; Gao J; Hou Y; Jiang M; Bai G
[Ad] Endereço:State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China.
[Ti] Título:Comparison and evaluation of antimuscarinic and anti-inflammatory effects of five Bulbus fritillariae species based on UPLC-Q/TOF integrated dual-luciferase reporter assay, PCA and ANN analysis.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1041-1042:60-69, 2017 Jan 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Many species of Bulbus fritillariae are used as traditional medicines for thousands of years; however, their application is not standardized. To clarify the differences and homologies, the antimuscarinic and anti-inflammatory effects of five BM species were firstly tested and compared at cellular level. With an integrated strategy combining UPLC-Q/TOF MS, PCA and ANN analysis, the active ingredients among 28 different chemical markers were predicted and identified. SB and QB extracts showed the best antimuscarinic effects and several steroidal alkaloids, such as solanidine, contributed to this effects. However, ZB was superior to reduce the inflammatory response. Another five components were responsible by decreasing the expression of NF-κB, including puqiedine, zhepeiresinol, 2-monopalmitin, N-demethylpuqietinone, and isoverticine. More novelty, a new cluster of five BM species based on active ingredients as potential quality markers was depicted to illustrate their functions. These results of the study could make a reference for the medicinal application of BM species in clinic; and the integrated strategy provided an effective method to obtain the quality markers from medical herbs, which was helpful for the quality control of traditional medicinal products.
[Mh] Termos MeSH primário: Anti-Inflamatórios
Fritillaria/química
Antagonistas Muscarínicos
NF-kappa B/antagonistas & inibidores
Extratos Vegetais
Receptor Muscarínico M2/antagonistas & inibidores
[Mh] Termos MeSH secundário: Anti-Inflamatórios/química
Anti-Inflamatórios/metabolismo
Anti-Inflamatórios/farmacologia
Biomarcadores/análise
Biomarcadores/metabolismo
Cromatografia Líquida de Alta Pressão/métodos
Diosgenina
Células HEK293
Seres Humanos
Luciferases/metabolismo
Espectrometria de Massas
Simulação de Acoplamento Molecular
Antagonistas Muscarínicos/química
Antagonistas Muscarínicos/metabolismo
Antagonistas Muscarínicos/farmacologia
NF-kappa B/análise
NF-kappa B/metabolismo
Extratos Vegetais/química
Extratos Vegetais/metabolismo
Extratos Vegetais/farmacologia
Análise de Componente Principal
Receptor Muscarínico M2/química
Receptor Muscarínico M2/metabolismo
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Biomarkers); 0 (Muscarinic Antagonists); 0 (NF-kappa B); 0 (Plant Extracts); 0 (Receptor, Muscarinic M2); EC 1.13.12.- (Luciferases); K49P2K8WLX (Diosgenin); W7801OHM8B (solanidine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170309
[Lr] Data última revisão:
170309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161225
[St] Status:MEDLINE



página 1 de 139 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde