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1.
Br J Pharmacol ; 151(6): 860-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17533426

RESUMO

BACKGROUND AND PURPOSE: In this work, a neuroactive peptide from the venom of the neotropical wasp Polybia occidentalis was isolated and its anti-nociceptive effects were characterized in well-established pain induction models. EXPERIMENTAL APPROACH: Wasp venom was analysed by reverse-phase HPLC and fractions screened for anti-nociceptive activity. The structure of the most active fraction was identified by electron-spray mass spectrometry (ESI-MS/MS) and it was further assessed in two tests of anti-nociceptive activity in rats: the hot plate and tail flick tests. KEY RESULTS: The most active fraction contained a peptide whose structure was Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH, which corresponds to that of Thr(6)-BK, a bradykinin analogue. This peptide was given by i.c.v. injection to rats. In the tail flick test, Thr(6)-BK induced anti-nociceptive effects, approximately twice as potent as either morphine or bradykinin also given i.c.v. The anti-nociceptive activity of Thr(6)-BK peaked at 30 min after injection and persisted for 2 h, longer than bradykinin. The primary mode of action of Thr(6)-BK involved the activation of B(2) bradykinin receptors, as anti-nociceptive effects of Thr(6)-BK were antagonized by a selective B(2) receptor antagonist. CONCLUSIONS AND IMPLICATIONS: Our data indicate that Thr(6)-BK acts through B(2) bradykinin receptors in the mammalian CNS, evoking antinociceptive behaviour. This activity is remarkably different from that of bradykinin, despite the structural similarities between both peptides. In addition, due to the increased metabolic stability of Thr(6)-BK, relative to that of bradykinin, this peptide could provide a novel tool in the investigation of kinin pathways involved with pain.


Assuntos
Analgésicos/farmacologia , Bradicinina/análogos & derivados , Dor/tratamento farmacológico , Venenos de Vespas/química , Analgésicos/administração & dosagem , Animais , Bradicinina/administração & dosagem , Bradicinina/isolamento & purificação , Bradicinina/farmacologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Sistema Calicreína-Cinina , Masculino , Morfina/administração & dosagem , Morfina/farmacologia , Dor/fisiopatologia , Medição da Dor , Ratos , Ratos Wistar , Receptor B2 da Bradicinina/efeitos dos fármacos , Receptor B2 da Bradicinina/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
2.
Brain Res Bull ; 55(1): 79-86, 2001 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-11427341

RESUMO

A number of neurotoxins derived from arthropod venoms are known to show highly selective effects on nervous tissue. These neurotoxins have been proved to be extremely useful tools to investigate either convulsive or anticonvulsive mechanisms in the nervous system. In the present work, intracerebroventricular injection of the crude venom from the spider Parawixia bistriata (Araneae, Araneidae) in rats induced convulsive limbic seizures (head and forelimb myoclonus, as well as rearing and falling). Neuroethological analysis showed that the limbic seizures induced by the venom were different from those induced by kainic acid. Intravenous injection of the same venom did not induce seizures, but the neuroethological analysis showed an intensification of grooming behavior similar to a displaced activity. In conclusion, our experiments point that crude venom of P. bistriata may contain convulsant neurotoxins probably acting in limbic system structures. The mechanism of action of these neurotoxins may be different from simple activation of glutamatergic kainate receptors, as evidenced by a comparative neuroethological analysis of seizures induced by either venom or kainic acid.


Assuntos
Comportamento Animal/efeitos dos fármacos , Ácido Caínico/farmacologia , Sistema Límbico/efeitos dos fármacos , Convulsões/induzido quimicamente , Venenos de Aranha/toxicidade , Animais , Comportamento Animal/fisiologia , Sistema Límbico/fisiopatologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Wistar , Receptores de Ácido Caínico/efeitos dos fármacos , Receptores de Ácido Caínico/metabolismo , Convulsões/fisiopatologia , Design de Software
3.
Brain Res Bull ; 52(6): 581-8, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10974500

RESUMO

The inhibition of excitatory mechanisms by components of low molecular weight, isolated from spiders and solitary wasps, such as, the acyl-polyamines, has demonstrated, on the one hand, neuroprotection potential, and on the other hand, it is well known that some arthropod venom components have convulsant activity. While many sophisticated experiments are conducted to determine the mechanisms and effects of arthropod venoms, relatively little attention has been paid to the behavioral changes that occur in mammals after being administered given doses of them. The precise detection of these behavioral changes can be used as a sensitive indicator of central nervous system dysfunction. This study investigated the behavioral effects of crude venom from the spider Scaptocosa raptoria after intracerebroventricular injection in male Wistar rats. The venom induced behavioral changes quantified using a neuroethological method, which allows the evaluation of the following parameters: frequency, duration, and strength of statistical association (chi-square) between pairs of behaviors. The rats exhibited a period of freezing, which was always followed by procursive-type seizures (running, gyrating, atonic falling, and jumping).


Assuntos
Comportamento Animal/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Venenos de Aranha/toxicidade , Aranhas/metabolismo , Animais , Comportamento Animal/fisiologia , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Injeções Intraventriculares , Masculino , Ratos , Ratos Wistar
4.
J Biochem Mol Toxicol ; 14(2): 88-94, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10630422

RESUMO

Glutamate (L-glu) is the most important excitatory neurotransmitter in the mammalian central nervous system. Its action is terminated by transporters located in the plasma membrane of neurons and glial cells, which have a critical role in preventing glutamate excitotoxicity under normal conditions. The neurotransmitter gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system. Venoms of solitary wasps and orb-spiders are composed of large proteins, medium-size peptides, polyamine amides (PAs), and other neuroactive components that are highly selective to nervous tissues. The abnormal operation of uptake systems is involved in several failures. Several studies indicate alterations in extracellular GABA and glutamate concentrations in epilepsy conditions that may relate to transporter functions. The effects of the crude and boiled venom of the social wasp Agelaia vicina, "cassununga," on GABA and L-glu uptake in rat cerebral cortex synaptosomes are related. The venom uncompetitively inhibited high- and low-affinity GABA uptake by 91.2% and by 76%, respectively. This kind of inhibition was also found to affect high- (99.6%) and low-affinity (90%) uptake of L-glu. These results suggest that the effects observed in these experiments indicate the venom of A. vicina to be a useful tool to further characterize GABA- and L-glu-uptake systems.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Sinaptossomos/efeitos dos fármacos , Venenos de Vespas/toxicidade , Ácido gama-Aminobutírico/metabolismo , Animais , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar , Sinaptossomos/metabolismo
6.
Rev Soc Bras Med Trop ; 29(4): 373-6, 1996.
Artigo em Português | MEDLINE | ID: mdl-8768588

RESUMO

We relate a case of an 18-year-old man, resident of Xapuri (state of Acre, Brazil), with a history of repeated episodes of meningoencephalitis (three in one year), each one was examined by a local doctor. In our service (Emílio Ribas Institute of Infectology) we observed a patient with polyjoint aches, radiological and bronchoscopic pulmonary alterations (without clinical features), meningeal and brain stem manifestations--with normal brain computed tomography and cerebrospinal fluid. Blood eosinophils and serological Toxocara canis test (ELISA) were greatly increased. With the hypothesis of Toxocariasis (visceral larva migrans) we administered thiabendazole that brought complete clinical and laboratory remission. Inspite of a new episode of headache with meningeal manifestation approximately one month later (treated with dexamethasone resulting in a full remission after three days) we have not found other manifestations in approximately three and a half years of ambulatory care.


Assuntos
Larva Migrans Visceral/diagnóstico , Toxocara canis , Adolescente , Animais , Anticorpos Anti-Helmínticos/sangue , Antinematódeos/administração & dosagem , Brasil , Doença Crônica , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Larva Migrans Visceral/complicações , Larva Migrans Visceral/tratamento farmacológico , Masculino , Recidiva , Tiabendazol/administração & dosagem , Toxocara canis/imunologia
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