Neurochemical Characterization of a Neuroprotective Compound fromParawixia bistriataSpider 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 ϭ 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 ϩ , K ϩ , and Ca 2ϩ channels, GABA B receptors, or ␥-aminobutyrate:␣-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.

Pro- and Anticonvulsant Effects of the Ant Dinoponera quadriceps (Kempf) Venom in Mice

“…Several other studies on invertebrate venoms have showed the anticonvulsant and neuroprotective activities of compounds in several animal models of seizure induction and neuronal damage (see Rajendra et al 2004, Mortari et al 2007. This inhibitory activity might be attributed to the selective antagonism of glutamatergic receptors (conantoxin-L; Jimenez et al 2002), blockage of Na + channels (BmK AS toxin; Zhao et al 2011), blockage of Ca 2+ channels (omega-conotoxin MVIIC and omega-agatoxin IVA; Jackson & Scheideler 1996), inhibition of glutamate release (PnTx3-6 toxin; Vieira et al 2003), enhancement of glutamate transporters (Fontana et al 2003(Fontana et al , 2007, or the inhibition of GABA and glycine transporters (Parawixin 1; Beleboni et al 2006).…”

Enhancing Glutamate Transport: Mechanism of Action of Parawixin1, a Neuroprotective Compound from Parawixia bistriata Spider Venom

“…Although compounds from spider and wasp venoms that inhibit neurotransmitter transport have been identified (for examples, see Pizzo et al, 2004;Beleboni et al, 2006;Lovelace et al, 2006), Parawixin1 is the first agent that seems to act directly on a glutamate transporter to increase uptake (Fontana et al, 2003). To establish the transporter subtype targeted by Parawixin1 and its mechanism of action, we evaluated its effects on glutamate uptake in COS-7 cells transfected with each of the three major CNS EAAT subtypes, as well as on native carriers reconstituted into proteoliposomes.…”

Neurotoxinas: Perspectivas para a descoberta de novos analgésicos

“…Mais recentemente, a estrutura química desse composto foi elucidada juntamente com parte do seu mecanismo de ação. Tratase de um composto pequeno, de estrutura análoga à do GABA, sendo que esta molécula não altera a atividade dos canais de Na + , K + e Ca ++ nem possui efeito sobre receptores de GABA, sobre a GABA transaminase ou sobre transporte reverso (BELEBONI et al, 2006). Apesar de encorajadores, os resultados obtidos com o estudo dos compostos de baixo peso molecular do veneno da aranha P. bistriata são preliminares.…”