Base de dados : MEDLINE
Pesquisa : D12.776.543.750.695.550 [Categoria DeCS]
Referências encontradas : 993 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 100 ir para página                         

  1 / 993 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29176874
[Au] Autor:Reyes-Corona D; Vázquez-Hernández N; Escobedo L; Orozco-Barrios CE; Ayala-Davila J; Moreno MG; Amaro-Lara ME; Flores-Martinez YM; Espadas-Alvarez AJ; Fernandez-Parrilla MA; Gonzalez-Barrios JA; Gutierrez-Castillo ME; González-Burgos I; Martinez-Fong D
[Ad] Endereço:Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Ciudad de México, México.
[Ti] Título:Neurturin overexpression in dopaminergic neurons induces presynaptic and postsynaptic structural changes in rats with chronic 6-hydroxydopamine lesion.
[So] Source:PLoS One;12(11):e0188239, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The structural effect of neurturin (NRTN) on the nigrostriatal dopaminergic system in animals remains unknown, although NRTN has been shown to be effective in Parkinson's disease animal models. Herein, we aimed to demonstrate that NRTN overexpression in dopaminergic neurons stimulates both neurite outgrowths in the nigrostriatal pathway and striatal dendritic spines in aging rats with chronic 6-hydroxydopamine (6-OHDA) lesion. At week 12 after lesion, pTracer-mNRTN-His or pGreenLantern-1 plasmids were intranigrally transfected using the NTS-polyplex nanoparticles system. We showed that the transgenic expression in dopaminergic neurons remained until the end of the study (12 weeks). Only animals expressing NRTN-His showed recovery of tyrosine hydroxylase (TH)+ cells (28 ± 2%), their neurites (32 ± 2%) and the neuron-specific cytoskeletal marker ß-III-tubulin in the substantia nigra; striatal TH(+) fibers were also recovered (52 ± 3%), when compared to the healthy condition. Neurotensin receptor type 1 levels were also significantly recovered in the substantia nigra and striatum. Dopamine recovery was 70 ± 4% in the striatum and complete in the substantia nigra. The number of dendritic spines of striatal medium spiny neurons was also significantly increased, but the recovery was not complete. Drug-activated circling behavior decreased by 73 ± 2% (methamphetamine) and 89 ± 1% (apomorphine). Similar decrease was observed in the spontaneous motor behavior. Our results demonstrate that NRTN causes presynaptic and postsynaptic restoration of the nigrostriatal dopaminergic system after a 6-OHDA-induced chronic lesion. However, those improvements did not reach the healthy condition, suggesting that NRTN exerts lesser neurotrophic effects than other neurotrophic approaches.
[Mh] Termos MeSH primário: Neurônios Dopaminérgicos/metabolismo
Neurturina/metabolismo
Terminações Pré-Sinápticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Corpo Estriado/metabolismo
Corpo Estriado/patologia
Citoesqueleto/metabolismo
Espinhas Dendríticas/metabolismo
Dopamina/metabolismo
Ensaio de Imunoadsorção Enzimática
Membro Anterior/fisiologia
Masculino
Camundongos
Neuritos/metabolismo
Oxidopamina
Ratos Wistar
Receptores de Neurotensina/metabolismo
Substância Negra/metabolismo
Substância Negra/patologia
Transfecção
Vibrissas/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurturin); 0 (Receptors, Neurotensin); 0 (neurotensin type 1 receptor); 8HW4YBZ748 (Oxidopamine); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188239


  2 / 993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28686721
[Au] Autor:Sharpe AL; Varela E; Beckstead MJ
[Ad] Endereço:Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, Texas, United States of America.
[Ti] Título:Systemic PD149163, a neurotensin receptor 1 agonist, decreases methamphetamine self-administration in DBA/2J mice without causing excessive sedation.
[So] Source:PLoS One;12(7):e0180710, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Methamphetamine (METH) is a psychostimulant that exhibits significant abuse potential. Although METH addiction is a major health and societal concern, no drug is currently approved for its therapeutic management. METH activates the central dopaminergic "reward" circuitry, and with repeated use increases levels of the neuromodulatory peptide neurotensin in the nucleus accumbens and ventral tegmental area. Previous studies in rats suggest that neurotensin agonism decreases METH self-administration, but these studies did not examine the effect of neurotensin agonism on the pattern of self-administration or open field locomotion. In our studies, we established intravenous METH self-administration in male, DBA/2J mice (fixed ratio 3, 2 hr sessions) and examined the effect of pretreatment with the NTS1 receptor agonist PD149163 on METH self-administration behavior. Locomotion following PD149163 was also measured up to 2 hours after injection on a rotarod and in an open field. Pretreatment with PD149163 (0.05 and 0.10 mg/kg, s.c.) significantly decreased METH self-administration. The pattern of responding suggested that PD149163 decreased motivation to self-administer METH initially in the session with more normal intake in the second hour of access. Voluntary movement in the open-field was significantly decreased by both 0.05 and 0.10 mg/kg (s.c.) PD149163 from 10-120 minutes after injection, but rotarod performance suggested that PD149163 did not cause frank sedation. These results suggest that a systemically delivered NTS1 receptor agonist decreases METH self-administration in mice. The pattern of self-administration suggests that PD149163 may acutely decrease motivation to self-administer METH before the drug is experienced, but cannot rule out that depression of voluntary movement plays a role in the decreased self-administration.
[Mh] Termos MeSH primário: Metanfetamina/toxicidade
Neurotensina/análogos & derivados
Neurotensina/metabolismo
Autoadministração/métodos
Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Dopamina/metabolismo
Seres Humanos
Camundongos
Camundongos Endogâmicos DBA
Neurotensina/administração & dosagem
Receptores de Neurotensina/metabolismo
Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (PD 149163); 0 (Receptors, Neurotensin); 39379-15-2 (Neurotensin); 44RAL3456C (Methamphetamine); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180710


  3 / 993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28510609
[Au] Autor:Huber S; Casagrande F; Hug MN; Wang L; Heine P; Kummer L; Plückthun A; Hennig M
[Ad] Endereço:Roche Innovation Center Basel, Pharmaceutical Research and Early Development, Basel, Switzerland.
[Ti] Título:SPR-based fragment screening with neurotensin receptor 1 generates novel small molecule ligands.
[So] Source:PLoS One;12(5):e0175842, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The neurotensin receptor 1 represents an important drug target involved in various diseases of the central nervous system. So far, the full exploitation of potential therapeutic activities has been compromised by the lack of compounds with favorable physicochemical and pharmacokinetic properties which efficiently penetrate the blood-brain barrier. Recent progress in the generation of stabilized variants of solubilized neurotensin receptor 1 and its subsequent purification and successful structure determination presents a solid starting point to apply the approach of fragment-based screening to extend the chemical space of known neurotensin receptor 1 ligands. In this report, surface plasmon resonance was used as primary method to screen 6369 compounds. Thereby 44 hits were identified and confirmed in competition as well as dose-response experiments. Furthermore, 4 out of 8 selected hits were validated using nuclear magnetic resonance spectroscopy as orthogonal biophysical method. Computational analysis of the compound structures, taking the known crystal structure of the endogenous peptide agonist into consideration, gave insight into the potential fragment-binding location and interactions and inspires chemistry efforts for further exploration of the fragments.
[Mh] Termos MeSH primário: Descoberta de Drogas
Receptores de Neurotensina/metabolismo
Bibliotecas de Moléculas Pequenas
[Mh] Termos MeSH secundário: Simulação por Computador
Descoberta de Drogas/métodos
Avaliação Pré-Clínica de Medicamentos
Seres Humanos
Cinética
Ligantes
Espectroscopia de Ressonância Magnética
Modelos Moleculares
Conformação Molecular
Ligação Proteica
Estabilidade Proteica
Receptores de Neurotensina/agonistas
Receptores de Neurotensina/antagonistas & inibidores
Receptores de Neurotensina/química
Reprodutibilidade dos Testes
Fluxo de Trabalho
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Receptors, Neurotensin); 0 (Small Molecule Libraries); 0 (neurotensin type 1 receptor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170517
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175842


  4 / 993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28494471
[Au] Autor:Dong Z; Lei Q; Yang R; Zhu S; Ke XX; Yang L; Cui H; Yi L
[Ad] Endereço:State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
[Ti] Título:Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a-3p/Bcl-w axis in glioblastoma.
[So] Source:Br J Cancer;116(12):1572-1584, 2017 Jun 06.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Backgroud:Glioblastoma is a kind of highly malignant and aggressive tumours in the central nervous system. Previously, we found that neurotensin (NTS) and its high-affinity receptor 1 (NTSR1) had essential roles in cell proliferation and invasiveness of glioblastoma. Unexpectedly, cell death also appeared by inhibition of NTSR1 except for cell cycle arrest. However, the mechanisms were remained to be further explored. METHODS: Cells treated with SR48692, a selective antagonist of NTSR1, or NTSR1 shRNA were stained with Annexin V-FITC/PI and the apoptosis was assessed by flow cytometry. Cytochrome c release was detected by using immunofluorescence. Mitochondrial membrane potential (MMP, ΔΨm) loss was stained by JC-1 and detected by immunofluorescence or flow cytometry. Apoptosis antibody array and microRNA microarray were performed to seek the potential regulators of NTSR1 inhibition-induced apoptosis. Interaction between let-7a-3p and Bcl-w 3'UTR was evaluated by using luciferase assay. RESULTS: SR48692 induced massive apoptosis, which was related to mitochondrial cytochrome c release and MMP loss. Knockdown of NTSR1 induced slight apoptosis and significant MMP loss. In addition, NTSR1 inhibition sensitised glioblastoma cells to actinomycin D or doxorubicin-induced apoptosis. Consistently, NTSR1 inhibition-induced mitochondrial apoptosis was accompanied by downregulation of Bcl-w and Bcl-2. Restoration of Bcl-w partly rescued NTSR1 deficiency-induced apoptosis. In addition, NTSR1 deficiency promoted higher let-7a-3p expression and inhibition let-7a-3p partly rescued NTSR1 inhibition-induced apoptosis. In addition, let-7a-3p inhibition promoted 3'UTR activities of Bcl-w and the expression of c-Myc and LIN28, which were the upstream of let-7a-3p, decreased after NTSR1 inhibition. CONCLUSIONS: NTSR1 had an important role in protecting glioblastoma from intrinsic apoptosis via c-Myc/LIN28/let-7a-3p/Bcl-w axis.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Glioblastoma/tratamento farmacológico
MicroRNAs/metabolismo
Receptores de Neurotensina/antagonistas & inibidores
Receptores de Neurotensina/genética
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Animais
Antibióticos Antineoplásicos/farmacologia
Proteínas Reguladoras de Apoptose/genética
Proteínas Reguladoras de Apoptose/metabolismo
Caspase 3/metabolismo
Linhagem Celular Tumoral
Citocromos c/metabolismo
Dactinomicina/farmacologia
Regulação para Baixo/efeitos dos fármacos
Doxorrubicina/farmacologia
Resistência a Medicamentos Antineoplásicos
Feminino
Técnicas de Silenciamento de Genes
Seres Humanos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Camundongos
Camundongos Nus
MicroRNAs/antagonistas & inibidores
MicroRNAs/genética
Mitocôndrias/metabolismo
Transplante de Neoplasias
Proteínas Proto-Oncogênicas c-bcl-2/genética
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Pirazóis/farmacologia
Quinolinas/farmacologia
RNA Interferente Pequeno/genética
Receptores de Neurotensina/metabolismo
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (Antibiotics, Antineoplastic); 0 (Apoptosis Regulatory Proteins); 0 (BCL2L2 protein, human); 0 (MicroRNAs); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Pyrazoles); 0 (Quinolines); 0 (RNA, Small Interfering); 0 (Receptors, Neurotensin); 0 (mirnlet7 microRNA, human); 0 (neurotensin type 1 receptor); 146362-70-1 (SR 48692); 1CC1JFE158 (Dactinomycin); 80168379AG (Doxorubicin); 9007-43-6 (Cytochromes c); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170512
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.126


  5 / 993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28368584
[Au] Autor:Fanelli R; Floquet N; Besserer-Offroy É; Delort B; Vivancos M; Longpré JM; Renault P; Martinez J; Sarret P; Cavelier F
[Ad] Endereço:Institut des Biomolécules Max Mousseron, IBMM, UMR-5247, CNRS, Université Montpellier, ENSCM , Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
[Ti] Título:Use of Molecular Modeling to Design Selective NTS2 Neurotensin Analogues.
[So] Source:J Med Chem;60(8):3303-3313, 2017 Apr 27.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neurotensin exerts potent analgesia by acting at both NTS1 and NTS2 receptors, whereas NTS1 activation also results in other physiological effects such as hypotension and hypothermia. Here, we used molecular modeling approach to design highly selective NTS2 ligands by investigating the docking of novel NT[8-13] compounds at both NTS1 and NTS2 sites. Molecular dynamics simulations revealed an interaction of the Tyr residue of NT[8-13] with an acidic residue (Glu ) located in the ECL2 of hNTS2 or with a basic residue (Arg ) at the same position in hNTS1. The importance of the residue at position 11 for NTS1/NTS2 selectivity was further demonstrated by the design of new NT analogues bearing basic (Lys, Orn) or acid (Asp or Glu) function. As predicted by the molecular dynamics simulations, binding of NT[8-13] analogues harboring a Lys exhibited higher affinity toward the hNTS1-R212E mutant receptor, in which Arg212 was substituted by the negatively charged Glu residue.
[Mh] Termos MeSH primário: Desenho de Drogas
Simulação de Dinâmica Molecular
Neurotensina/análogos & derivados
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Neurotensina/metabolismo
Receptores de Neurotensina/química
Receptores de Neurotensina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Neurotensin); 39379-15-2 (Neurotensin)
[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:170404
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.6b01848


  6 / 993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28341345
[Au] Autor:Besserer-Offroy É; Brouillette RL; Lavenus S; Froehlich U; Brumwell A; Murza A; Longpré JM; Marsault É; Grandbois M; Sarret P; Leduc R
[Ad] Endereço:Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4. Electronic address: Elie.Besserer-Offroy@USherbrooke.ca.
[Ti] Título:The signaling signature of the neurotensin type 1 receptor with endogenous ligands.
[So] Source:Eur J Pharmacol;805:1-13, 2017 Jun 15.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The human neurotensin 1 receptor (hNTS1) is a G protein-coupled receptor involved in many physiological functions, including analgesia, hypothermia, and hypotension. To gain a better understanding of which signaling pathways or combination of pathways are linked to NTS1 activation and function, we investigated the ability of activated hNTS1, which was stably expressed by CHO-K1 cells, to directly engage G proteins, activate second messenger cascades and recruit ß-arrestins. Using BRET-based biosensors, we found that neurotensin (NT), NT(8-13) and neuromedin N (NN) activated the Gα -, Gα -, Gα -, and Gα -protein signaling pathways as well as the recruitment of ß-arrestins 1 and 2. Using pharmacological inhibitors, we further demonstrated that all three ligands stimulated the production of inositol phosphate and modulation of cAMP accumulation along with ERK1/2 activation. Interestingly, despite the functional coupling to Gα and Gα , NT was found to produce higher levels of cAMP in the presence of pertussis toxin, supporting that hNTS1 activation leads to cAMP accumulation in a Gα -dependent manner. Additionally, we demonstrated that the full activation of ERK1/2 required signaling through both a PTX-sensitive G -c-Src signaling pathway and PLCß-DAG-PKC-Raf-1-dependent pathway downstream of G . Finally, the whole-cell integrated signatures monitored by the cell-based surface plasmon resonance and changes in the electrical impedance of a confluent cell monolayer led to identical phenotypic responses between the three ligands. The characterization of the hNTS1-mediated cellular signaling network will be helpful to accelerate the validation of potential NTS1 biased ligands with an improved therapeutic/adverse effect profile.
[Mh] Termos MeSH primário: Receptores de Neurotensina/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Células CHO
Cricetinae
Cricetulus
Ativação Enzimática
Proteínas de Ligação ao GTP/metabolismo
Seres Humanos
Ligantes
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Neurotensina/química
Neurotensina/metabolismo
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/metabolismo
beta-Arrestina 1/metabolismo
beta-Arrestina 2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Peptide Fragments); 0 (Receptors, Neurotensin); 0 (beta-Arrestin 1); 0 (beta-Arrestin 2); 0 (neurotensin type 1 receptor); 102577-25-3 (neuromedin N); 39379-15-2 (Neurotensin); 60482-95-3 (neurotensin (8-13)); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 3.6.1.- (GTP-Binding Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170326
[St] Status:MEDLINE


  7 / 993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28262417
[Au] Autor:Gantz SC; Bean BP
[Ad] Endereço:Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: stephanie.gantz@nih.gov.
[Ti] Título:Cell-Autonomous Excitation of Midbrain Dopamine Neurons by Endocannabinoid-Dependent Lipid Signaling.
[So] Source:Neuron;93(6):1375-1387.e2, 2017 Mar 22.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing. In voltage-clamp experiments, 2-AG reduced A-type potassium current (I ) through a cannabinoid receptor-independent mechanism mimicked by arachidonic acid, which has no activity on cannabinoid receptors. Activation of orexin, neurotensin, and metabotropic glutamate G -linked receptors mimicked the effects of exogenous 2-AG and their actions were prevented by inhibiting the 2-AG-synthesizing enzyme diacylglycerol lipase α. The results show that 2-AG and related lipid signaling molecules can directly tune neuronal excitability in a cell-autonomous manner by modulating I .
[Mh] Termos MeSH primário: Potenciais de Ação/fisiologia
Ácidos Araquidônicos/fisiologia
Neurônios Dopaminérgicos/fisiologia
Endocanabinoides/fisiologia
Glicerídeos/fisiologia
Potenciais da Membrana/fisiologia
Mesencéfalo/fisiologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Animais
Ácido Araquidônico/farmacologia
Ácidos Araquidônicos/farmacologia
Neurônios Dopaminérgicos/efeitos dos fármacos
Endocanabinoides/farmacologia
Feminino
Glicerídeos/farmacologia
Lipase Lipoproteica/antagonistas & inibidores
Masculino
Potenciais da Membrana/efeitos dos fármacos
Camundongos
Receptores de Orexina/agonistas
Receptores de Glutamato Metabotrópico/agonistas
Receptores de Neurotensina/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arachidonic Acids); 0 (Endocannabinoids); 0 (Glycerides); 0 (Orexin Receptors); 0 (Receptors, Metabotropic Glutamate); 0 (Receptors, Neurotensin); 27YG812J1I (Arachidonic Acid); 8D239QDW64 (glyceryl 2-arachidonate); EC 3.1.1.34 (Lipoprotein Lipase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE


  8 / 993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28254866
[Au] Autor:Schulz J; Rohracker M; Stiebler M; Goldschmidt J; Stöber F; Noriega M; Pethe A; Lukas M; Osterkamp F; Reineke U; Höhne A; Smerling C; Amthauer H
[Ad] Endereço:Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke Universität, Magdeburg, Germany.
[Ti] Título:Proof of Therapeutic Efficacy of a Lu-Labeled Neurotensin Receptor 1 Antagonist in a Colon Carcinoma Xenograft Model.
[So] Source:J Nucl Med;58(6):936-941, 2017 Jun.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Increased expression of neurotensin receptor 1 (NTR1) has been shown in a large number of tumor entities such as pancreatic or colon carcinoma. Hence, this receptor is a promising target for diagnostic imaging and radioligand therapy. Using the favorable biodistribution data of the NTR1-targeting agent In-3BP-227, we investigated the therapeutic effect of its Lu-labeled analog on the tumor growth of NTR1-positive HT29 colon carcinoma xenografts. 3BP-227 was labeled with Lu. To assess its biodistribution properties, SPECT and CT scans of HT29-xenografted nude mice injected with Lu-3BP-227 were acquired, and ex vivo tissue activity was determined. To evaluate therapeutic efficacy, 2 groups of mice received the radiopharmaceutical in a median dose of either 165 MBq (129-232 MBq, = 10) or 110 MBq (82-116 MBq, = 10), whereas control mice were injected with vehicle ( = 10). Tumor sizes and body weights were monitored for up to 49 d. Renal function and histologic morphology were evaluated. Whole-body SPECT/CT images allowed clear tumor visualization with low background activity and high tumor-to-kidney and -liver ratios. Ex vivo biodistribution data confirmed high and persistent uptake of Lu-3BP-227 in HT29 tumors (19.0 ± 3.6 vs. 2.7 ± 1.6 percentage injected dose per gram at 3 and 69 h after injection, respectively). The application of Lu-3BP-227 resulted in a distinct delay of tumor growth. Median tumor doubling time for controls was 5.5 d (interquartile range [IQR], 2.8-7.0), compared with 17.5 d (IQR, 5.5-22.5 d) for the 110-MBq and 41.0 d (IQR, 27.5-55.0) for the 165-MBg group. Compared with controls, median relative tumor volume at day 23 after injection was reduced by 55% ( = 0.034) in the 110-MBq and by 88% ( < 0.01) in the 165-MBq group. Renal histology and clinical chemistry results did not differ between radiotherapy groups and controls, suggesting absence of therapy-induced acute renal damage. These data demonstrate that the novel NTR1-targeting theranostic agent 3BP-227 is an effective and promising candidate for radioligand therapy, with a favorable preliminary safety profile and high potential for clinical translation.
[Mh] Termos MeSH primário: Neoplasias do Colo/diagnóstico por imagem
Neoplasias do Colo/radioterapia
Lutécio/uso terapêutico
Terapia de Alvo Molecular/métodos
Receptores de Neurotensina/antagonistas & inibidores
Nanomedicina Teranóstica/métodos
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos da radiação
Linhagem Celular Tumoral
Neoplasias do Colo/metabolismo
Neoplasias do Colo/patologia
Feminino
Células HT29
Seres Humanos
Camundongos
Camundongos Nus
Compostos Radiofarmacêuticos/uso terapêutico
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Radiopharmaceuticals); 0 (Receptors, Neurotensin); 0 (neurotensin type 1 receptor); 5H0DOZ21UJ (Lutetium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.116.185140


  9 / 993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28130052
[Au] Autor:Liu Q; Hazan A; Grinman E; Angulo JA
[Ad] Endereço:Department of Biological Sciences, Hunter College, United States; Department of Biochemistry, The Graduate Center of The City University of New York, United States.
[Ti] Título:Pharmacological activation of the neurotensin receptor 1 abrogates the methamphetamine-induced striatal apoptosis in the mouse brain.
[So] Source:Brain Res;1659:148-155, 2017 Mar 15.
[Is] ISSN:1872-6240
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Methamphetamine (METH) is a widely abused psychostimulant displaying potent addictive and neurotoxic properties. METH induces neurotoxicity of dopaminergic terminals and striatal neurons in the striatum. Despite much information on neurotransmitters, the role of neuropeptides is poorly understood. In this study, we investigated the role of the neuropeptide neurotensin on the METH-induced apoptosis of some striatal neurons in mice. We observed that a single injection of METH (30mg/kg, ip) induced the loss of approximately 15% of striatal neurons. An agonist of the neurotensin receptor 1 (PD149163, ip at various doses) attenuated the METH-induced striatal neuron apoptosis. Utilizing quantitative real time PCR, we showed that METH also up-regulated neurotensin gene expression with 96% increase in preproneurotensin mRNA levels in the striatum as compared to the control. Additionally, NTR1 agonist (ip injection) attenuated hyperthermia at 2h post-METH injection; hyperthermia is a putative and significant component of METH-induced neurotoxicity. To investigate the role of neurotensin without affecting core body temperature, we performed stereotactic injection of PD149163 into the striatum and observed that this compound maintained attenuated the METH-induced apoptosis in the striatum, while leaving core body temperature unaffected. There was no effect of NTR1 agonist on METH-induced dopamine terminal degeneration, as evidenced by tyrosine hydroxylase levels determined by Western blot. These data indicate that the neuropeptide neurotensin modulates the striatal neuronal apoptosis induced by METH through diverse mechanisms that need to be investigated. Furthermore, due to its neuroprotective properties, neurotensin receptor agonists show potential as drug candidates for the treatment of METH abuse and some neurological disorders.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Corpo Estriado/efeitos dos fármacos
Metanfetamina/toxicidade
Neurotensina/análogos & derivados
Neurotransmissores/farmacologia
Receptores de Neurotensina/agonistas
[Mh] Termos MeSH secundário: Animais
Apoptose/fisiologia
Estimulantes do Sistema Nervoso Central/toxicidade
Corpo Estriado/metabolismo
Corpo Estriado/patologia
Modelos Animais de Doenças
Avaliação Pré-Clínica de Medicamentos
Febre/induzido quimicamente
Febre/tratamento farmacológico
Febre/metabolismo
Febre/patologia
Masculino
Camundongos Endogâmicos ICR
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Neurônios/patologia
Fármacos Neuroprotetores/farmacologia
Neurotensina/metabolismo
Neurotensina/farmacologia
Precursores de Proteínas/metabolismo
RNA Mensageiro/metabolismo
Receptores de Neurotensina/metabolismo
Tirosina 3-Mono-Oxigenase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Central Nervous System Stimulants); 0 (Neuroprotective Agents); 0 (Neurotransmitter Agents); 0 (PD 149163); 0 (Protein Precursors); 0 (RNA, Messenger); 0 (Receptors, Neurotensin); 0 (neuromedin N precursor); 0 (neurotensin type 1 receptor); 39379-15-2 (Neurotensin); 44RAL3456C (Methamphetamine); EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170129
[St] Status:MEDLINE


  10 / 993 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28089664
[Au] Autor:Steele FF; Whitehouse SC; Aday JS; Prus AJ
[Ad] Endereço:Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States.
[Ti] Título:Neurotensin NTS and NTS receptor agonists produce anxiolytic-like effects in the 22-kHz ultrasonic vocalization model in rats.
[So] Source:Brain Res;1658:31-35, 2017 Mar 01.
[Is] ISSN:1872-6240
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Neurotensin is a neuropeptide neurotransmitter that interacts with multiple neurotransmitter systems, including those regulating amygdalar function, via NTS and NTS receptors. Both receptors are expressed in the amygdala and agonists for NTS or NTS receptors have exhibited anxiolytic effects in animal models. Systemic adminstration of NTS receptor agonist PD149163 was recently shown to reduce footshock conditioned 22-kHz ultrasonic vocalizations in rats, suggesting that PD149163 produced an anxiolytic effect. The effects that neurotensin may have or a selective NTS receptor agonist may have on 22-kHz vocalizations has yet to be examined. The current study evaluated the effects of intracerebroventricularly administered neurotensin (0.1-10.0µg), PD149163 (0.1-10.0ng), or the NTS receptor agonist JMV-431 (0.1-1.0µg) on footshock conditioned 22-kHz vocalizations in male Wistar rats. Neurotensin, PD149163, and JMV-431 all significantly reduced the number 22-kHz calls. No changes in call duration were found, suggesting that non-specific drug effects do not account for the reductions in 22-kHz calls. These data support anxiolytic effects produced by activation of NTS or NTS receptors, and suggest that neurotensin plays a natural role in the expression of conditioned USVs. These data suggest that both receptor subtypes are putative pharmacologic targets.
[Mh] Termos MeSH primário: Ansiolíticos/farmacologia
Neurotransmissores/farmacologia
Receptores de Neurotensina/agonistas
Vocalização Animal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Cateteres de Demora
Condicionamento (Psicologia)/efeitos dos fármacos
Condicionamento (Psicologia)/fisiologia
Relação Dose-Resposta a Droga
Avaliação Pré-Clínica de Medicamentos
Eletrochoque
Medo/efeitos dos fármacos
Medo/fisiologia

Infusões Intraventriculares
Masculino
Neurotensina/análogos & derivados
Neurotensina/farmacologia
Fragmentos de Peptídeos/farmacologia
Ratos Wistar
Receptores de Neurotensina/metabolismo
Estresse Psicológico/tratamento farmacológico
Estresse Psicológico/metabolismo
Ultrassom
Vocalização Animal/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Boc-Arg-Arg-Pro-Tyr-psi(CH2NH)-Ile-Leu); 0 (Neurotransmitter Agents); 0 (Ntsr2 protein, rat); 0 (PD 149163); 0 (Peptide Fragments); 0 (Receptors, Neurotensin); 0 (neurotensin type 1 receptor); 39379-15-2 (Neurotensin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170117
[St] Status:MEDLINE



página 1 de 100 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