Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eur J Pharmacol ; 889: 173589, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32961171

RESUMO

Neferine, a bisbenzylisoquinoline alkaloid present in Nelumbo nucifera, has been reported to exhibit neuroprotective effects. Because reduced glutamatergic transmission through inhibition of glutamate release has been proposed as a mechanism of neuroprotection, we investigated whether and how neferine inhibits glutamate release in the nerve terminals of the cerebral cortex of rats. The results demonstrated that neferine inhibits the glutamate release that is evoked by the potassium channel blocker 4-aminopyridine, doing so in a dose-dependent manner. This effect was prevented by removing extracellular calcium and blocking vesicular transporters or N- and P/Q-type calcium channels but not by blocking glutamate transporters. Neferine decreased the 4-aminopyridine-stimulated elevation in intrasynaptosomal calcium concentration; however, it had no effect on the synaptosomal membrane potential. The inhibition of glutamate release by neferine was also eliminated by the selective 5-hydroxytryptamine 1A (5HT1A) receptor antagonist WAY100635, Gi/o protein inhibitor pertussis toxin, adenylyl cyclase inhibitor MDL12330A, and protein kinase A inhibitor H89. Moreover, immunocytochemical analysis revealed the presence of 5-HT1A receptor proteins in the vesicular transporter of glutamate type 1 positive synaptosomes. The molecular docking study also demonstrated that neferine exhibited the highest binding affinity with 5-HT1A receptors (Autodock scores for 5-HA1A = -11.4 kcal/mol). Collectively, these results suggested that neferine activates 5-HT1A receptors in cortical synaptosomes, which decreases calcium influx and glutamate release through the activation of Gi/o protein and the inhibition of adenylyl cyclase/cAMP/protein kinase A cascade.


Assuntos
Benzilisoquinolinas/farmacologia , Córtex Cerebral/metabolismo , Ácido Glutâmico/metabolismo , Nelumbo , Terminações Nervosas/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Benzilisoquinolinas/química , Benzilisoquinolinas/isolamento & purificação , Córtex Cerebral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Antagonistas de Aminoácidos Excitatórios/química , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Simulação de Acoplamento Molecular , Terminações Nervosas/efeitos dos fármacos , Estrutura Secundária de Proteína , Ratos , Ratos Sprague-Dawley , Receptor 5-HT1A de Serotonina/química
2.
Neurotoxicology ; 80: 105-111, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32702364

RESUMO

The inhibitory glycine receptor (GlyR) is a key mediator of synaptic signalling in spinal cord, brain stem, and higher centres of the central nervous system. We examined the glycinergic activity of sarcophine (SN), a marine terpenoid known for its various biological activities, and its trans-diol derivative (7S, 8R)-dihydroxy-deepoxysarcophine (DSN). SN was isolated from the Red Sea soft coral Sacrophyton glaucum, DSN was semisynthesized by hydrolysis of the epoxide ring. In cytotoxicity tests against HEK293 cells, SN and DSN had LD50 values of 29.3 ± 3.0 mM and 123.5 ± 13.0 mM, respectively. Both compounds were tested against recombinant human α1 glycine receptors in HEK293 cells using whole-cell recording techniques. Both, SN and DSN were shown for the first time to be inhibitors of recombinant glycine receptors, with KIvalues of 2.1 ± 0.3 µM for SN, and 109 ± 9 µM for DSN. Receptor inhibition was also studied in vivo in a mouse model of strychnine toxicity. Surprisingly, in mouse experiments strychnine inhibition was not augmented by either terpenoid. While DSN had no significant effect on strychnine toxicity, SN even delayed strychnine effects. This could be accounted for by assuming that strychnine and sarcophine derivatives compete for the same binding site on the receptor, so the less toxic sarcophine can prevent strychnine from binding. The combination of modulatory activity and low level of toxicity makes sarcophines attractive structures for novel glycinergic drugs.


Assuntos
4-Butirolactona/análogos & derivados , Antozoários/metabolismo , Encéfalo/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Receptores de Glicina/antagonistas & inibidores , Convulsões/prevenção & controle , 4-Butirolactona/síntese química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , 4-Butirolactona/toxicidade , Animais , Sítios de Ligação , Ligação Competitiva , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/síntese química , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Antagonistas de Aminoácidos Excitatórios/toxicidade , Células HEK293 , Humanos , Masculino , Camundongos , Ligação Proteica , Receptores de Glicina/genética , Receptores de Glicina/metabolismo , Convulsões/induzido quimicamente , Convulsões/metabolismo , Convulsões/fisiopatologia , Estricnina
3.
Biomed Pharmacother ; 106: 1031-1038, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30119168

RESUMO

An imbalance between excitatory and inhibitory neurotransmitters is known to induce neuronal excitotoxicity which is a major cause of neurodegenerative disorders. Excessive glutamate concentration leads to the neuronal death by increasing oxidative stress and affecting the apoptotic signaling pathway. We investigated the anti-excitotoxic effects and associated working mechanisms of 30% ethanol extract of Aquilariae Lignum (ALE) against hippocampal neuronal death by glutamate. HT22 cells were treated with glutamate (20 mM) for 24 h following pretreatment with ALE (5, 10, 25 µg/mL). Cell viability, biochemical analysis, flow chemistry, and Western blotting assays were performed. Glutamate treatment substantially increased the intracellular level of reactive oxygen species (ROS) and Ca2+ influx into the cell, which were followed by apoptosis. ALE pretreatment, however, significantly attenuated these excitotoxicity-related features according to the results of Annexin V analysis and the lactate dehydrogenase assay, in which the calpain pathway (in a caspase 3-independent manner) may be involved. ALE pretreatment also significantly attenuated the glutamate-induced activation of both inflammation-associated molecules (extracellular signal-regulated kinase, c-Jun N-terminal kinases and p38) and death-related molecules (p53, apoptosis-inducing factor). The inactivation of brain-derived neurotrophic factor (BDNF) was restored by ALE pretreatment. Our results verified that A. Lignum has potential neuroprotective effects on glutamate-induced excitotoxicity in hippocampal neuron cells, and its underlying mechanism may involve the regulation of ROS-mediated cell death pathways.


Assuntos
Agonistas de Aminoácidos Excitatórios/toxicidade , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/toxicidade , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Thymelaeaceae , Animais , Apoptose/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Calpaína/metabolismo , Linhagem Celular , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Espécies Reativas de Oxigênio/metabolismo , Thymelaeaceae/química , Fatores de Tempo
4.
Biomed Khim ; 63(1): 27-31, 2017 Jan.
Artigo em Russo | MEDLINE | ID: mdl-28251948

RESUMO

Cortexin, a drug containing hydrolyzed brain peptides, has long been used in clinics, but the mechanisms of its action remain obscure. We have hypothesized that cortexin-related neuroprotection is associated with the ability of the drug to inhibit brain proteases. Cortexin effectively inhibited brain caspase-8, while its effects on caspase-1, -3, -9, cathepsin B and calpain were much less pronounced or absent. In addition, we isolated a peptide fraction from cortexin holding all the inhibitory capacity of the original drug, but with a much more simple composition. Both cortexin and its fraction prevented neuronal damage in a culture model of glutamate-induced cell death. Neuroprotective effect of Cortexin may be mediated by inhibition of the initiator caspase-8 in the brain.


Assuntos
Caspase 8/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Inibidores de Proteases/farmacologia , Hidrolisados de Proteína/química , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Química Encefálica , Calpaína/genética , Calpaína/metabolismo , Caspase 1/genética , Caspase 1/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 9/genética , Caspase 9/metabolismo , Catepsina B/genética , Catepsina B/metabolismo , Bovinos , Morte Celular/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Expressão Gênica , Ácido Glutâmico/toxicidade , Neurônios/citologia , Neurônios/enzimologia , Fármacos Neuroprotetores/isolamento & purificação , Cultura Primária de Células , Inibidores de Proteases/isolamento & purificação , Ratos , Ratos Wistar
5.
Bull Exp Biol Med ; 162(4): 430-432, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28239790
6.
Drug Test Anal ; 7(8): 708-13, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25487525

RESUMO

Analysis of decomposed skeletal tissues for dextromethorphan (DXM) and dextrorphan (DXT) using microwave assisted extraction (MAE), microplate solid-phase extraction (MPSPE) and gas chromatography-mass spectrometry (GC-MS) is described. Rats (n = 3) received 100 mg/kg DXM (i.p.) and were euthanized by CO2 asphyxiation roughly 20 min post-dose. Remains decomposed to skeleton outdoors and vertebral bones were recovered, cleaned, and pulverized. Pulverized bone underwent MAE using methanol as an extraction solvent in a closed microwave system, followed by MPSPE and GC-MS. Analyte stability under MAE conditions was assessed and found to be stable for at least 60 min irradiation time. The majority (>90%) of each analyte was recovered after 15 min. The MPSPE-GCMS method was fit to a quadratic response (R(2) > 0.99), over the concentration range 10-10 000 ng⋅mL(-1) , with coefficients of variation <20% in triplicate analysis. The MPSPE-GCMS method displayed a limit of detection of 10 ng⋅mL(-1) for both analytes. Following MAE for 60 min (80 °C, 1200 W), MPSPE-GCMS analysis of vertebral bone of DXM-exposed rats detected both analytes in all samples (DXM: 0.9-1.5 µg⋅g(-1) ; DXT: 0.5-1.8 µg⋅g(-1) ).


Assuntos
Osso e Ossos/química , Dextrometorfano/análise , Dextrorfano/análise , Antagonistas de Aminoácidos Excitatórios/análise , Toxicologia Forense/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Animais , Dextrometorfano/isolamento & purificação , Dextrorfano/isolamento & purificação , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Limite de Detecção , Masculino , Micro-Ondas , Ratos Wistar , Extração em Fase Sólida/métodos
8.
PLoS One ; 7(5): e37080, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22606332

RESUMO

Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha), also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6) and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty.


Assuntos
Ácido Glutâmico/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Withania , Animais , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Antagonistas de Aminoácidos Excitatórios/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Degeneração Neural/prevenção & controle , Moléculas de Adesão de Célula Nervosa/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Neurotoxinas/antagonistas & inibidores , Neurotoxinas/toxicidade , Extratos Vegetais/farmacologia , Folhas de Planta , Plantas Medicinais , Ratos , Tretinoína/farmacologia
9.
J Ethnopharmacol ; 137(1): 382-8, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21669274

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Several Searsia species (Anacardiaceae), including Searsia dentata and Searsia pyroides, are used in South Africa traditional medicine to treat epilepsy. Ethanol leaf extracts of these plants have been shown to act as possible antagonists of N-methyl-d-aspartate (NMDA)-type glutamate receptors. MATERIALS AND METHODS: Leaf material of three Searsia species were collected from the Botanical Garden at the University of KwaZulu-Natal, Pietermaritzburg; dried and extracted with ethanol in an ultrasound bath. Filtered and dried extracts were resuspended in DMSO (100mg/ml) and diluted in the recording solution. The effect of Searsia dentata, Searsia pyroides and Searsia glauca extracts was investigated in dissociated cerebellar granule cells (CGCs) from 8-day-old rats and in transiently transfected HEK (human embryonic kidney) 293 cells (HEK), expressing either NR1a/NR2A or NR1a/NR2B receptors. In both systems we measured whole-cell currents elicited by 0.5mM NMDA (CGCs) or 50 µM glutamic acid (HEK) at -60 mV in 0Mg and 30 µM glycine and NMDA driven Ca influx in Fura2-loaded CGC. RESULTS: Searsia dentata and Searsia pyroides ethanol extracts caused a dose-dependent decrease of NR current with ED(50) close to 0.03 mg/ml in CGC and a similar inhibition (80% with 1mg/ml) in HEK cells, while Searsia glauca was much less effective. The inhibition was dependent on time of incubation and slightly favored by opening of the NR channel. It was hardly reversible during the recording time, but was not caused by accelerated run-down or by interaction with the modulatory redox site. Searsia pyroides ethanol extract also depressed the NMDA stimulated increase in intracellular Ca. CONCLUSIONS: The data confirm the specificity of Searsia dentata and Searsia pyroides and justify their use in traditional medicine. These plants may combine one or more γ-aminobutyric acid (GABA)(A) agonists with one or more NMDA antagonists, thus representing an efficient treatment for epilepsy.


Assuntos
Anticonvulsivantes/farmacologia , Cerebelo/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Extratos Vegetais/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Rhus , Animais , Anticonvulsivantes/química , Anticonvulsivantes/isolamento & purificação , Sinalização do Cálcio/efeitos dos fármacos , Cerebelo/metabolismo , Relação Dose-Resposta a Droga , Etanol/química , Antagonistas de Aminoácidos Excitatórios/química , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Células HEK293 , Humanos , Medicinas Tradicionais Africanas , Potenciais da Membrana , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Rhus/química , Solventes/química , Fatores de Tempo , Transfecção
10.
J Pharm Biomed Anal ; 42(5): 543-8, 2006 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-16860510

RESUMO

The aim of this work was to obtain the direct optical resolution of a new glutamate receptor antagonist ((p-chloro)1-aryl-6,7,-dimethoxy-1,2,3,4-tetrahydroisoquinoline, PS3), by liquid chromatography on Chiralcel OD column. A response surface methodology (RSM) was employed to optimize the enantiomeric separation of the racemate with the lowest number of experiments; in particular, a face-centred design (FCD) was applied to evaluate the influence of critical parameters on the experimental response. Furthermore, in order to find the best compromise between several responses, a multicriteria decision-making approach, the Derringer's desirability function, was successful to simultaneously optimize the responses resolution and migration times of the two enantiomers. The proposed LC method provided the baseline enantioseparation of the investigated drug. 9.3% (v/v) ethanol added to n-hexane as mobile phase, 1.0 mL min(-1) flow rate, and 18 degrees C column temperature were the optimum experimental conditions allowing to achieve the highest enantioresolution of PS3 in less than 17 min.


Assuntos
Cromatografia Líquida/métodos , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Modelos Químicos , Tetra-Hidroisoquinolinas/isolamento & purificação , Antagonistas de Aminoácidos Excitatórios/química , Estrutura Molecular , Estereoisomerismo , Tetra-Hidroisoquinolinas/química
11.
Toxicol Lett ; 144(2): 205-12, 2003 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-12927364

RESUMO

The protective effect of ethanol extract from the fruits of Alpinia oxyphylla on glutamate-induced neuronal apoptosis was examined in primary cultured mouse cortical neurons. After exposure of cortical neurons to 30 microM glutamate for 24 h, cortical neurons exhibited remarkable apoptotic-like death as evidenced by multi-indices including morphological features, cell viability assay, DNA fragmentation on agarose gel and flow cytometric analysis. Co-treatment of the neurons with A. oxyphylla fruits extract (AFEx) (80-200 microg/ml) in the presence of glutamate significantly elevated cell viability, reduced the number of apoptotic cells and decreased the intensity of glutamate-induced DNA fragmentation. These results suggest the neuroprotective potential of A. oxyphylla fruits against glutamate-induced neuronal apoptosis.


Assuntos
Alpinia/química , Apoptose/efeitos dos fármacos , Córtex Cerebral/citologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Fragmentação do DNA , Eletroforese em Gel de Ágar , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Citometria de Fluxo , Frutas/química , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/ultraestrutura , Fármacos Neuroprotetores/isolamento & purificação , Extratos Vegetais/farmacologia
12.
Neurosignals ; 12(1): 31-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12624526

RESUMO

Traditional Chinese medicine (TCM) has a long history in stroke therapy and its therapeutic efficacy has been confirmed by clinical studies. The molecular basis of the neuroprotective effects is unknown. We wondered whether or not the neuroprotective effect of TCMs might be due to their N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist properties. We used the patch-clamp technique to screen 22 TCM stroke drugs for NMDAR antagonist activity in cultured cortical neurons. The drugs were also screened for their ability to abate NMDA-induced neurotoxicity. Aqueous extracts of Scutellaria baicalensis, Stephania tetrandra, and Salvia miltiorrhiza blocked currents induced by NMDA (200 microM, 10 microM glycine, 0 Mg2+) at a holding potential of -80 mV by 83.45+/-4.34, 38.65+/-7.50, and 52.97+/-1.78%, respectively. The block of the NMDA-evoked currents was voltage-dependent and showed a negative slope conductance reminiscent of Mg2+. Atomic absorption spectrophotometry revealed the presence of 12.5, 2, and 8.7 mM Mg2+ in the extracts of S. baicalensis,S. tetrandra, and S. miltiorrhiza, respectively. None of these extracts blocked NMDA-induced neuronal death. The Uncaria rhynchophylla extract blocked NMDA-evoked currents by 54.98+/-8.61% even at +60 mV and reduced NMDA-induced neuronal death by 59.13+/-3.52%. NMDAR antagonist activity may underlie the neuroprotective effects of this TCM. Some TCM drugs may exert therapeutic effects due to their Mg2+ content.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Animais , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Embrião de Mamíferos , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Camundongos , Estruturas Vegetais , Receptores de N-Metil-D-Aspartato/fisiologia
14.
J Neurosci Res ; 40(6): 797-806, 1995 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-7629892

RESUMO

One of the endogenous substances which modulate glutamate receptor binding was isolated and highly purified from porcine brain. The purification involved extraction of brain tissue with doubled distilled water, followed by gel filtration, anion exchange, cation exchange, and several steps of C18 reverse-phase high performance liquid chromatography (HPLC). A low molecular weight glutamate binding inhibitor (LGBI) was purified to apparent homogeneity as judged from the elution profile of an HPLC column, in which a symmetrical peak was obtained when the eluate was monitored at 220 nm. The LGBI appears to be a small molecule (< 2 kD) that is heat- and acid/base-stable. The highly purified LGBI has no effect on GABAA and benzodiazepine receptor binding. The LGBI is not L-glutamate, L-aspartate or other negatively charged endogenous substances, since they are clearly separated from the LGBI in anion exchange chromatography. The inhibitory effect of the LGBI on [3H]L-glutamate binding is reversible, and it only changes the Bmax while the Kd remains the same. Since the membrane preparations used for [3H]L-glutamate binding assays for the detection of LGBI activity were enriched with quisqualate (QA)-sensitive subtypes, it was suggested that the LGBI could be a modulator of the QA receptor. Some amino acids which produce significant inhibition of glutamate binding activity were also compared with the LGBI, and they all showed no resemblance to the LGBI. The chemical structure of the LGBI remains to be determined.


Assuntos
Fatores Biológicos/isolamento & purificação , Encéfalo/metabolismo , Aminoácidos/farmacologia , Animais , Fatores Biológicos/química , Cisteína/farmacologia , Estabilidade de Medicamentos , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Ácido Glutâmico/metabolismo , Glutamina/farmacologia , Membranas/metabolismo , Peso Molecular , Receptores de Glutamato/efeitos dos fármacos , Receptores de Glutamato/metabolismo , Suínos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...