RESUMO
Brain-derived neurotrophic factor (BDNF) is a neurotrophin of marked commercial, scientific, diagnostic, and therapeutic interest. The preservation of its structural cystine-knot is the main challenge in its industrial production. A suitable expression system is critical to achieve the most efficient production of bioactive and stable BDNF for pharmaceutical purposes.
RESUMO
OBJECTIVES: The erythrinan alkaloids erythravine and 11α-hydroxy-erythravine from Erythrina verna (Vell.) have been extensively investigated for their anxiolytic and anticonvulsant effects. Both are structurally similar to the erythrartine that also exhibit anxiolytic effects, but there is no report on its anticonvulsant potential. Since some anxiolytic drugs can be useful in the management of epileptic seizures, we investigated whether erythrartine could prevent seizures induced by different chemoconvulsants. METHODS: Experiments were performed using different concentrations of erythrartine injected via intracerebroventricular in rats submitted to pilocarpine, kainic acid, pentylenetetrazol or picrotoxin-induced seizures. Moreover, the rotarod test was performed to verify the effects of erythrartine on animal motor coordination. RESULTS: Our data showed for the first time that erythrartine prevented the occurrence of seizures induced by all of the chemoconvulsants tested and did not affect locomotor performance neither produced sedative effect on animals. CONCLUSION: Obtained results validate the ethnopharmacological significance of E. verna and provide new information on erythrartine, another erythrinian alkaloid of biotechnological and medicinal interest.
Assuntos
Alcaloides/uso terapêutico , Anticonvulsivantes/uso terapêutico , Erythrina/química , Fitoterapia , Extratos Vegetais/uso terapêutico , Convulsões/prevenção & controle , Alcaloides/farmacologia , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Anticonvulsivantes/farmacologia , Convulsivantes , Modelos Animais de Doenças , Epilepsia/tratamento farmacológico , Masculino , Extratos Vegetais/farmacologia , Ratos Wistar , Convulsões/induzido quimicamenteRESUMO
Erythrinian alkaloids ((+)-erythravine and (+)-11-α-hydroxy-erythravine) have been pointed as the main responsible agents for the anticonvulsant and anxiolytic properties of Erythrina mulungu Mart ex Benth. The present work provides a new set of information about the mode of action of these alkaloids by the use of a complementary approach of neurochemical and electrophysiological assays. We propose here that the antiepileptic and anxiolytic properties exhibited by both alkaloids appear not to be related to the inhibition of glutamate binding or GABA uptake, or even to the increase of glutamate uptake or GABA binding, as investigated here by the use of rat cortical synaptosomes. Similarly, and even in a high concentration, (+)-erythravine and (+)-11-α-hydroxy-erythravine did not modulate the main sodium and potassium channel isoforms checked by the use of voltage-clamp studies on Xenopus laevis oocytes. However, unlike (+)-11-α-hydroxy-erythravine, which presented a little effect, it was possible to observe that the (+)-erythravine alkaloid produced a significant inhibitory modulation on α4ß2, α4ß4 and α7 isoforms of nicotinic acetylcholine receptors also checked by the use of voltage-clamp studies, which could explain at least partially its anxiolytic and anticonvulsant properties. Since (+)-11-α-hydroxy-erythravine and (+)-erythravine modulated nicotinic acetylcholine receptors to different extents, it is possible to reinforce that small differences between the chemical structure of these alkaloids can affect the selectivity and affinity of target-ligand interactions, conferring distinct potency and/or pharmacological properties to them, as previously suggested by differential experimental comparison between different erythrinian alkaloids.
Assuntos
Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Erythrina/química , Ácido Glutâmico/metabolismo , Antagonistas Nicotínicos/farmacologia , Oócitos , Técnicas de Patch-Clamp , Potássio/metabolismo , Receptores Nicotínicos/efeitos dos fármacos , Canais de Sódio/metabolismo , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Xenopus laevis , Ácido gama-Aminobutírico/metabolismoRESUMO
Different types of epilepsy and forms of pathological anxiety have been described as significant neurological disorders that may exist as comorbidities. Some of those disorders share the association of affected limbic areas/neuropathological triggers as well as the use of drugs for their clinical management. The aim of this work was to investigate the anticonvulsant and anxiolytic properties of the vitexin (apigenin-8-C-glucoside), since this compound is a flavonoid usually found as one of the major constituents in several medicinal plants claimed as anxiolytics and/or anticonvulsants. This investigation was performed by the use of a series of classical murine animal models of chemically induced-seizures and of anxiety-related tests (open-field, elevated plus-maze, and light-dark box tests). Here, we show that the systemic administration of vitexin (1.25; 2.5 and 5 mg/kg; i.p.) exhibited selective protection against chemically-induced seizures. Vitexin did not block seizures evoked by glutamate receptors agonists (NMDA and kainic acid), and it did not interfere with the latencies for these seizures. Conversely, the same treatments protected the animals in a dose-dependent manner against the seizures evoked by the Gabaergic antagonists picrotoxin and PTZ and rise the latency time for the first seizure on non-protected animals. The higher dose of vitexin protected 100% of animals against the tonic-clonic seizures triggered by GABA antagonists. The results from open-field, elevated plus-maze, and light-dark box tests indicated the anxiolytic properties of vitexin at similar range of doses described for the anticonvulsant action screening. Furthermore, these results pointed that vitexin did not cause sedation or locomotor impairment on animals. The selective action of vitexin against picrotoxin and PTZ may reinforce the hypothesis by which this compound acts mainly by the modulation of GABAergic neurotransmission and/or related pathways. This could be useful to explain the dual activity of vitexin as anticonvulsant and anxiolytic, and highlight the pharmacological interest on this promising flavonoid.
RESUMO
Arthropod venoms are sources of molecules that may be useful tools to investigate molecular mechanisms of putative new medicines and laboratory drugs. Here we show the effects of the compound agelaiatoxin-8 (AVTx8), isolated from Agelaia vicina venom, on γ-aminobutyric acid (GABA) neurotransmission in rat brain synaptosomes. Analysis reveals that AvTx8 is composed by 14 amino acid residues with a molecular weight (MW) of 1567 Da. AvTx8 increased GABA release and inhibited GABA uptake in synaptosomes from rat cerebral cortex. AvTx8 inhibited GABA uptake and increased GABA release in the presence of Ca+ , Na+ , and K+ channel blockers, suggesting that it acts directly on GABA transporters. In addition, AvTx8 significantly decreases GABA binding in synaptic membranes from rat brain cortex, suggesting that it also modulates the activity of GABA receptors. Moreover, AvTx8 decreased GAT-1- and GAT-3-mediated GABA uptake in transfected COS-7 cells. Accordingly, we suggest that AvTx8 modulates GABA neurotransmission and might provide a novel entry point for identifying a new class of GABA-modulating neuroprotective drugs.
Assuntos
Membranas Sinápticas/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Sinaptossomos/metabolismo , Venenos de Vespas , Vespas/química , Ácido gama-Aminobutírico/metabolismo , Animais , Células COS , Chlorocebus aethiops , Canais Iônicos/antagonistas & inibidores , Canais Iônicos/metabolismo , Ratos , Ratos Wistar , Membranas Sinápticas/patologia , Sinaptossomos/patologia , Venenos de Vespas/química , Venenos de Vespas/isolamento & purificação , Venenos de Vespas/toxicidadeRESUMO
Haemonchus contortus is an important gastrointestinal parasite on sheep farms in tropical regions. The resistance of the parasite against most anthelmintic drugs represents a great economic problem to sheep farming and is a major challenge that needs to be overcome. The searches for new anthelmintic agents that act on different stages of the parasite's life cycle are necessary for the development of new therapeutic options. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of Thymus vulgaris essential oil against H. contortus and of its main component, the monoterpene thymol. Despite the relative ineffectiveness of the oil in the in vivo test, which may be corrected in the future after technical improvements to increase the oil's bioavailability, the in vitro results validated the popular use of T. vulgaris oil as an anthelmintic agent, at least against H. contortus. In fact, both the essential oil and thymol, which accounts for 50.22% of the oil composition, were effective against the three main stages of H. contortus. The oil and thymol were able to inhibit egg hatching by 96.4-100%, larval development by 90.8-100%, and larval motility by 97-100%. Similar to the positive control (levamisole 20mg/mL), the oil and thymol completely inhibited the motility of H. contortus adults within the first 8h of the experiment. Since thymol reproduces the anthelmintic effects of the oil and because it is the main component of the oil, it is reasonable to assume that thymol is the most important compound responsible for the anthelmintic effect of T. vulgaris. These results are of ethnopharmacological importance and may contribute to the development of new drugs and even herbal medicines, increasing treatment options for the farm breeding.
Assuntos
Anti-Helmínticos/farmacologia , Hemoncose/tratamento farmacológico , Haemonchus/efeitos dos fármacos , Óleos Voláteis/farmacologia , Doenças dos Ovinos/tratamento farmacológico , Thymus (Planta)/química , Animais , Modelos Animais de Doenças , Etnofarmacologia , Hemoncose/parasitologia , Hemoncose/veterinária , Larva , Levamisol/farmacologia , Masculino , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Ovinos , Doenças dos Ovinos/parasitologia , Timol/farmacologiaRESUMO
Five monoterpenes naturally occurring in essential oils were tested for their insecticidal and repellent activities against the bruchid beetle Callosobruchus maculatus and the maize weevil Sitophilus zeamais. The monoterpenes were highly efficient as inducers of mortality or repellency against both insect species. They were more efficient in their fumigant activity against C. maculatus than against S. zeamais, while this profile of action was inverted when considering the repellent activities. Eugenol was one the most effective fumigants against both insects and one the most effective repellent against C. maculatus, while citronellal and geranial were one the most effective repellents against S. zeamais. Functional and positional isomerism of the monoterpenes pairs appears to exert little or no influence on theirs effects, especially in case of repellency. The validation of the insecticidal/repellent efficacy of isolated monoterpenes may permit a more advantageous, rapid, economic and optimized approach to the identification of promising oils for commercial formulations when combined with ethnobotanical strategies.
Assuntos
Repelentes de Insetos/farmacologia , Inseticidas/farmacologia , Monoterpenos/farmacologia , Monoterpenos Acíclicos , Aldeídos/farmacologia , Animais , Besouros , Grão Comestível/parasitologia , Eugenol/farmacologia , Fumigação , Controle de Insetos , Óleos Voláteis/farmacologia , Terpenos/farmacologia , GorgulhosRESUMO
Contamination of preharvest and stored peanuts (Arachis hypogaea L.) by aflatoxigenic strains of Aspergillus flavus is an important economical and food safety problem in many tropical and subtropical areas of the world. The present investigation reports the antifungal activity of a halitoxins/amphitoxins enriched extract obtained from the sponge Amphimedon sp. (HAEEAsp), and of batzelladine L isolated from the sponge Monanchora arbuscula on Aspergillus flavus isolated from stored peanuts. A PCR system directed against the ITS region and aflatoxin biosynthetic pathway genes of A. flavus was applied for identification of aflatoxin producing strains. The HAEEAsp extract and batzelladine L showed minimal inhibitory concentration (MIC) in the range between 1.9 to 15.6 microg/mL and between 1.9 to 7.8 microg/mL, respectively. The minimal fungicide concentration (MFC) of HAEEAsp extract and batzelladine L was in the range between 3.9 to 31.3 microg/mL and 3.9 to 15.6 microg/mL, respectively. These results indicate that these marine alkaloids may be further explored for the development of potential lead compounds active against aflatoxigenic fungi.
Assuntos
Antifúngicos/análise , Aspergillus flavus/efeitos dos fármacos , Poríferos/química , Animais , Antifúngicos/farmacologia , Arachis/microbiologia , Testes de Sensibilidade Microbiana , Poríferos/metabolismoRESUMO
Cancer is commonly diagnosed in dogs over the age of 10 and is a leading cause of death due to the lack of effective drugs. Flavonoids possess antioxidant, anti-inflammatory and anticarcinogenic properties and have been studied as chemopreventive agents in human cancer therapy. However, the literature on dogs is sparse. In this study, we analyzed the effect of nine flavonoids on cell viability, DNA damage and topoisomerase IIa/IIb gene expression in a canine tumor cell line (DH82). Apigenin, luteolin, trans-chalcone and 4-methoxychalcone showed the highest degree of cytotoxicity in the absence of considerable DNA damage, whereas genistein exhibited low cytotoxicity but induced a high level of DNA damage. These five flavonoids inhibited topoisomerase IIa and IIb gene expression to variable extents and with variable specificity. Genistein exerted a lower inhibitory effect on the two topoisomerases than luteolin and apigenin. trans-Chalcone and 4-methoxychalcone exerted greater inhibition of topoisomerase IIa expression than topoisomerase IIb. The differences in the effects between genistein and luteolin and apigenin might be explained by the position of ring B, whereas the more specific effect of chalcones on topoisomerase IIa might be due to their open chain structure.
Assuntos
Flavonoides/farmacologia , Sarcoma Histiocítico/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , DNA Topoisomerases Tipo II/genética , Cães , Flavonoides/química , Flavonoides/toxicidade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sarcoma Histiocítico/genética , Concentração Inibidora 50 , Estrutura Molecular , Inibidores da Topoisomerase/química , Inibidores da Topoisomerase/farmacologia , Inibidores da Topoisomerase/toxicidadeRESUMO
The aims of the present work were to investigate the effects of the repeated administration of Parawixin2 (2-amino-5-ureidopentanamide; formerly FrPbAII), a novel GABA and glycine uptake inhibitor, in rats submitted to PTZ-induced kindling. Wistar rats were randomly divided in groups (n=6-8) for different treatments. Systemic injections of PTZ were administered every 48 h in the dose of 33 mg/kg; i.p., that is sufficient to induce fully kindled seizures in saline i.c.v. treated rats in a short period of time (28 days). Treatments in two types of positive controls (diazepam - DZP and nipecotic acid - NA groups) consisted in daily systemic injections of DZP (2mg/kg; i.p.) or i.c.v. injections of NA (12 µg/µL), while in experimental groups in daily i.c.v. injections of different doses of Parawixin2 (0.15; 0.075; 0.015 µg/µL). Seizures were analyzed using the Lamberty & Klitgaard score and kindling was considered as established after at least three consecutive seizures of score 4 or 5. Cumulative seizure scores for each group were analyzed using repeated measures of ANOVA followed by Tukey test. PTZ induced 4 and 5-score seizures after 12 injections in saline treated rats, whereas daily injection of Parawixin2 inhibited the onset of seizures in a dose dependent manner. Also, the challenging administration of PTZ did not raise seizure score in animals treated with the highest dose of Parawixin2 or those treated with DZP or NA. These findings together with previous data from our laboratory show that Parawixin2 could be a useful probe to design new antiepileptic drugs.
Assuntos
Anticonvulsivantes/farmacologia , Convulsivantes , Inibidores da Captação de GABA/farmacologia , Excitação Neurológica , Pentilenotetrazol , Venenos de Aranha/química , Ureia/análogos & derivados , Animais , Anticonvulsivantes/uso terapêutico , Diazepam/farmacologia , Diazepam/uso terapêutico , Relação Dose-Resposta a Droga , Inibidores da Captação de GABA/uso terapêutico , Masculino , Ácidos Nipecóticos/farmacologia , Ácidos Nipecóticos/uso terapêutico , Ratos , Ratos Wistar , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Ureia/farmacologia , Ureia/uso terapêuticoRESUMO
OBJECTIVES: The purpose of the present work was to characterize the pharmacological profile of different L. alba chemotypes and to correlate the obtained data to the presence of chemical constituents detected by phytochemical analysis. METHODS: Essential oils from each L. alba chemotype (LP1-LP7) were characterized by gas chromatography-mass spectrometry (GC-MS) and extracted non-volatile compounds were analysed by HPLC and GC-MS. The anticonvulsant actions of the extracted compounds were studied in pentylenetetrazole-induced clonic seizures in mice and their effect on motor coordination was studied using the rota-rod test in rats. The synaptosomes and synaptic membranes of the rats were examined for the influence of LP3 chemotype extract on GABA uptake and binding experiments. KEY FINDINGS: Behavioural parameters encompassed by the pentylenetetrazole test indicated that 80% ethanolic extracts of LP1, LP3 and LP6 L. alba chemotypes were more effective as anticonvulsant agents. Neurochemical assays using synaptosomes and synaptic membranes showed that L. alba LP3 chemotype 80% ethanolic extract inhibited GABA uptake and GABA binding in a dose-dependent manner. HPLC analysis showed that LP1, LP3 and LP6 80% ethanolic extracts presented a similar profile of constituents, differing from those seen in LP2, LP4, LP5 and LP7 80% ethanolic extracts, which exhibited no anticonvulsant effect. GC-MS analysis indicated the occurrence of phenylpropanoids in methanolic fractions obtained from LP1, LP3 and LP6 80% ethanolic extracts and also the accumulation of inositol and flavonoids in hydroalcoholic fractions. CONCLUSIONS: Our results suggest that the anticonvulsant properties shown by L. alba might be correlated to the presence of a complex of non-volatile substances (phenylpropanoids, flavonoids and/or inositols), and also to the volatile terpenoids (beta-myrcene, citral, limonene and carvone), which have been previously validated as anticonvulsants.
Assuntos
Anticonvulsivantes/uso terapêutico , Flavonoides/uso terapêutico , Lippia/química , Óleos Voláteis/uso terapêutico , Convulsões/tratamento farmacológico , Terpenos/uso terapêutico , Animais , Anticonvulsivantes/farmacologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Camundongos , Destreza Motora/efeitos dos fármacos , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Pentilenotetrazol , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Ratos , Ratos Wistar , Teste de Desempenho do Rota-Rod , Convulsões/induzido quimicamente , Terpenos/farmacologia , Ácido gama-Aminobutírico/metabolismoRESUMO
Although the number of science and engineering (S&E) publications produced in Latin America grew exponentially over the past 15 years, the investment in science and the number of full time researchers did not grow at a comparable rate. Moreover, Latin American science is handicapped by constrained resources and access to information, higher costs of research, English-language barriers and brain-drain. One possible explanation for the observed rise in paper numbers, therefore, is that Latin American scientists have increased production, perhaps at the cost of quality. As an alternative, Latin America authors may have increased production while maintaining quality (e.g., through creativity, intense work and enhancement of international cooperation). Our aim is to verify which of these interpretations best applies for the field of comparative biochemistry and physiology (CBP). To achieve this goal, we compared the impact indicators of two randomly selected samples of authors (n=20; all with 8 to 30 years of scientific production), one from Latin America and another from developed countries. For additional comparison, we included also a group of twelve highly cited and recognized CBP researchers. We used Hirsch's indexes (h and m) as main indicators of performance, but compared also classical bibliometric indexes such as total number of citations, total number of papers and the ratio of citation per paper (CpP). The mean of most indexes were not significantly different between the two groups of regular CBP researchers, except for CpP, which was 1.7-fold higher in authors from developed countries. As expected, both groups had mean indicators well below those from the sample of highly cited researchers (average h values for top and regular CBP researchers were 37.3+/-3.0 and 11.4+/-0.9, respectively). Considering that Hirsch's indexes are more suitable indicators of performance than CpP, we conclude that Latin American CBP researchers, despite handicaps, perform similarly to those in developed countries. The forth special issue of Comparative Biochemistry and Physiology ("The Face of Latin American Comparative Biochemistry and Physiology") celebrates, with 24 new manuscripts from Brazil, Mexico, Argentina and Chile, the diversity of biological science in Latin America.
Assuntos
Bibliometria , Bioquímica/tendências , Pesquisa Biomédica/tendências , Fisiologia/tendências , Bioquímica/educação , Pesquisa Biomédica/educação , Pesquisa Biomédica/estatística & dados numéricos , Bases de Dados Bibliográficas , América Latina , Fisiologia/educação , PublicaçõesRESUMO
Phospholipases A2 (PLA2s) are commonly found in snake venoms from Viperidae, Hydrophidae and Elaphidae families and have been extensively studied due to their pharmacological and physiopathological effects in living organisms. This article reports a review on natural and artificial inhibitors of enzymatic, toxic and pharmacological effects induced by snake venom PLA2s. These inhibitors act on PLA2s through different mechanisms, most of them still not completely understood, including binding to specific domains, denaturation, modification of specific amino acid residues and others. Several substances have been evaluated regarding their effects against snake venoms and isolated toxins, including plant extracts and compounds from marine animals, mammals and snakes serum plasma, in addition to poly or monoclonal antibodies and several synthetic molecules. Research involving these inhibitors may be useful to understand the mechanism of action of PLA2s and their role in envenomations caused by snake bite. Furthermore, the biotechnological potential of PLA2 inhibitors may provide therapeutic molecular models with antiophidian activity to supplement the conventional serum therapy against these multifunctional enzymes.
Assuntos
Fosfolipases A/antagonistas & inibidores , Venenos de Serpentes/enzimologia , Animais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Humanos , Modelos Moleculares , Fosfolipases A2RESUMO
In this work we describe the isolation of a new l-amino acid oxidase (LAAO) referred to as BpirLAAO-I from Bothrops pirajai snake venom, which was highly purified using a combination of molecular exclusion, affinity, and hydrophobic chromatography steps. BpirLAAO-I homodimeric acid glycoprotein (approximate Mr and pI of 130,000 and 4.9, respectively) displays high specificity toward hydrophobic/aromatic amino acids, while deglycosylation does not alter its enzymatic activity. The N-terminal LAAO sequence of its first 49 amino acids presented a high similarity between a amino acid sequence with other LAAOs from: Bothrops spp., Crotalus spp., Calloselasma rhodostoma, Agkistrodon spp., Trimeresurus spp., Pseudechis australis, Oxyuranus scutellatus, and Notechis scutatus. BpirLAAO-I induces time-dependent platelet aggregation, mouse paw edema, cytotoxic activity against Escherichia coli, Pseudomonas aeruginosa, Leishmania sp., and tumor cells, and also a typical fago (M13mp18) DNA fragmentation. Platelet aggregation, leishmanicidal and antitumoral activities were reduced by catalase. Thus, BpirLAAO-I is a multifunctional protein with promising biotechnological and medical applications.
Assuntos
Antibacterianos , Bothrops , Venenos de Crotalídeos/química , L-Aminoácido Oxidase , Sequência de Aminoácidos , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Catálise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Edema/induzido quimicamente , Humanos , L-Aminoácido Oxidase/química , L-Aminoácido Oxidase/isolamento & purificação , L-Aminoácido Oxidase/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Agregação Plaquetária/efeitos dos fármacos , Fatores de TempoRESUMO
We obtained a neurotoxic fraction (AcTx) from star fruit (Averrhoa carambola) and studied its effects on GABAergic and glutamatergic transmission systems. AcTx had no effect on GABA/glutamate uptake or release, or on glutamate binding. However, it specifically inhibited GABA binding in a concentration-dependent manner (IC(50)=0.89muM). Video-electroencephalogram recordings demonstrated that following cortical administration of AcTx, animals showed behavioral changes, including tonic-clonic seizures, evolving into status epilepticus, accompanied by cortical epileptiform activity. Chemical characterization of AcTx showed that this compound is a nonproteic molecule with a molecular weight less than 500, differing from oxalic acid. This neurotoxic fraction of star fruit may be considered a new tool for neurochemical and neuroethological research.
Assuntos
Química Encefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Convulsivantes/toxicidade , Magnoliopsida/química , Neurotoxinas/toxicidade , Extratos Vegetais/toxicidade , Animais , Ligação Competitiva , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Química Encefálica/fisiologia , Convulsivantes/isolamento & purificação , Epilepsia/induzido quimicamente , Epilepsia/metabolismo , Epilepsia/fisiopatologia , Frutas/química , Ácido Glutâmico/metabolismo , Masculino , Camundongos , Peso Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurotoxinas/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/metabolismo , Ensaio Radioligante , Ratos , Ratos Wistar , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismoRESUMO
It has previously been shown that the denatured crude extract of Agelaia vicina wasp venom inhibits glutamate and GABA uptake in rat cerebral cortex synaptosomes. To identify the components responsible for these effects, the neurotoxin AvTx 7 (molecular weight of 1210 Da) was isolated from A. vicina venom and its effects on glutamate neurotransmission investigated. AvTx 7 inhibits glutamate uptake in a dose-dependent and uncompetitive manner. AvTx 7 was found to stimulate the glutamate release in the presence of calcium and sodium channel blockers, suggesting that its action is not mediated through these channels. AvTx 7 potentiates glutamate release in the presence of K(+) channel blockers tetraethylammonium and 4-aminopyridine, indicating that the toxin may act through these drugs-sensible K(+) channels. We suggest that AvTx 7 can be a valuable tool to enhance our understanding of K(+) channels' involvement in the release of glutamate.