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Purification of a neuroprotective component of Parawixia bistriata spider venom that enhances glutamate uptake
Journal article   Open access   Peer reviewed

Purification of a neuroprotective component of Parawixia bistriata spider venom that enhances glutamate uptake

Andréia Cristina Karklin Fontana, Renato Guizzo, Renê de Oliveira Beleboni, Antonio Renato Meirelles E Silva, Norberto Cysne Coimbra, Susan G Amara, Wagner Ferreira dos Santos and Joaquim Coutinho-Netto
British journal of pharmacology, v 139(7), pp 1297-1309
Aug 2003
DOI: https://doi.org/10.1038/sj.bjp.0705352
PMID: 12890709
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1038/sj.bjp.0705352View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Animals Brazil Carbon Isotopes Cerebral Cortex - cytology Chromatography, High Pressure Liquid - methods Chromatography, Ion Exchange Disease Models, Animal Dose-Response Relationship, Drug gamma-Aminobutyric Acid - drug effects gamma-Aminobutyric Acid - pharmacokinetics gamma-Aminobutyric Acid - secretion Glaucoma - drug therapy Glaucoma - physiopathology Glutamic Acid - drug effects Glutamic Acid - pharmacokinetics Glutamic Acid - secretion Ion Channels - drug effects Ion Channels - metabolism Ion Channels - physiopathology Male Neuroprotective Agents - chemistry Neuroprotective Agents - isolation & purification Neuroprotective Agents - pharmacology Rats Rats, Wistar Receptors, Metabotropic Glutamate - drug effects Receptors, Metabotropic Glutamate - physiology Retina - drug effects Retina - pathology Retina - ultrastructure Spider Venoms - chemistry Spider Venoms - isolation & purification Spider Venoms - pharmacology Spiders Synaptosomes - drug effects Synaptosomes - secretion Tissue Extracts - pharmacology Tritium
(1) In this study, we examined the effects of crude venom from the spider Parawixia bistriata on glutamate and GABA uptake into synaptosomes prepared from rat cerebral cortex. Addition of venom to cortical synaptosomes stimulated glutamate uptake and inhibited GABA uptake in a concentration-dependent manner. (2) The venom was fractionated using reverse-phase high-performance liquid chromatography on a preparative column. The fraction that retained glutamate uptake-stimulating activity was further purified on a reverse-phase analytical column followed by ion-exchange chromatography. (3) The active fraction, referred to as PbTx1.2.3, stimulated glutamate uptake in synaptosomes without changing the K(M) value, and did not affect GABA uptake. Additional experiments showed that the enhancement of glutamate uptake by PbTx1.2.3 occurs when ionotropic glutamate receptors or voltage-gated sodium and calcium channels are completely inhibited or when GABA receptors and potassium channels are activated, indicating that the compound may have a direct action on the transporters. (4) In an experimental model for glaucoma in which rat retinas are subjected to ischemia followed by reperfusion, PbTx1.2.3 protected neurons from excitotoxic death in both outer and inner nuclear layers, and ganglion cell layers. (5) This active spider venom component may serve as a basis for designing therapeutic drugs that increase glutamate clearance and limit neurodegeneration.

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Web of Science research areas
Pharmacology & Pharmacy
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