Neurochemical characterization of a neuroprotective compound from Parawixia bistriata spider venom that inhibits synaptosomal uptake of GABA and glycine.

Abstract

The major contribution of this work is the isolation of a neuroprotective compound referred to as 2-amino-5-ureidopentanamide (FrPbAII) (M(r) = 174) from Parawixia bistriata spider venom and an investigation of its mode of action. FrPbAII inhibits synaptosomal GABA uptake in a dose-dependent manner and probably does not act on Na(+), K(+), and Ca(2+) channels, GABA(B) receptors, or gamma-aminobutyrate:alpha-ketoglutarate aminotransferase enzyme; therefore, it is not directly dependent on these structures for its action. Direct increase of GABA release and reverse transport are also ruled out as mechanisms of FrPbAII activities as well as unspecific actions on pore membrane formation. Moreover, FrPbAII is selective for GABA and glycine transporters, having slight or no effect on monoamines or glutamate transporters. According to our experimental glaucoma data in rat retina, FrPbAII is able to cross the blood-retina barrier and promote effective protection of retinal layers submitted to ischemic conditions. These studies are of relevance by providing a better understanding of neurochemical mechanisms involved in brain function and for possible development of new neuropharmacological and therapeutic tools.

• Authors: Renê Oliveira Beleboni, Renato Guizzo, Andréia Cristina Karklin Fontana, Andrea Baldocchi Pizzo, Ruither Oliveira Gomes Carolino, Leonardo Gobbo-Neto, Norberto Peporine Lopes, Joaquim Coutinho-Netto, Wagner Ferreira Dos Santos
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 69 Issue 6 Pg. 1998-2006 (Jun 2006) ISSN: 0026-895X [Print] United States
• PMID: 16551783 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-amino-5-ureidopentanamide
• GABA Plasma Membrane Transport Proteins
• GABA-B Receptor Agonists
• Glycine Plasma Membrane Transport Proteins
• Ion Channels
• Neuroprotective Agents
• Spider Venoms
• gamma-Aminobutyric Acid
• Urea
• Glycine

Topics

• Animals
• Biological Transport (drug effects)
• GABA Plasma Membrane Transport Proteins (drug effects)
• GABA-B Receptor Agonists
• Glaucoma (prevention & control)
• Glycine (metabolism)
• Glycine Plasma Membrane Transport Proteins (drug effects)
• Ion Channels (antagonists & inhibitors)
• Male
• Neuroprotective Agents (isolation & purification, pharmacology)
• Rats
• Rats, Inbred BB
• Retina (drug effects)
• Spider Venoms (chemistry)
• Spiders (metabolism)
• Synaptosomes (drug effects, metabolism)
• Urea (analogs & derivatives, isolation & purification, pharmacology)
• gamma-Aminobutyric Acid (metabolism)