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

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.

Effects of microinjections of neurotoxin AvTx8, isolated from the social wasp Agelaia vicina (Hymenoptera, Vespidae) venom, on GABAergic nigrotectal pathways.

Several investigations have provided information that defensive behaviors evoked by stimulation of deep layers of the superior colliculus (dlSC) are subjected to inhibitory nigral modulation. This inhibition is made mainly through GABAergic neurons from substantia nigra, pars reticulata (SNpr), that sends outputs toward neural networks of the deep layers of the superior colliculus and dorsal periaqueductal gray matter involved with the organization of fear-like responses. In this work, we compared the effects of two GABAergic agonists, muscimol and baclofen, with the effect of neurotoxin AvTx8 (1567 Da), isolated from the venom of the social wasp Agelaia vicina, microinjected into SNpr of Rattus norvegicus (Wistar rats) prior to dlSC saline or bicuculline microinjections, considering that wasp venom has some influence on the uptake of GABA and/or glutamate neurotransmitters. GABA(A) receptor blockade in the dlSC evoked a vigorous escape behavior, expressed by rapid running, jumps and turns, as compared to control. These defensive reactions were maximized after the intranigral GABA(A) agonism with muscimol, but not after in situ GABA(B) agonism. Nigral microinjection of AvTx8 induced similar effects to those of baclofen, decreasing the intensity of behavioral defensive reactions caused by GABA(A) receptor blockade in the dorsal mesencephalon. These findings suggest that AvTx8 has some effects on GABAergic neurotransmission, increasing the activity of the inhibitory nigro-collicular pathways, causing an anti-panic (antiaversive) effect. Therefore, our work suggests AvTx8 as a novel pharmacological tool to study differences between the two types of GABAergic receptors and excitatory amino acid-mediated mechanisms in the brain and brainstem networks.

Pharmacological and biochemical aspects of GABAergic neurotransmission: pathological and neuropsychobiological relationships.

1. The GABAergic neurotransmission has been implicated in the modulation of many neural networks in forebrain, midbrain and hindbrain, as well as, in several neurological disorders. 2. The complete comprehension of GABA system neurochemical properties and the search for approaches in identifying new targets for the treatment of neural diseases related to GABAergic pathway are of the extreme relevance. 3. The present review will be focused on the pharmacology and biochemistry of the GABA metabolism, GABA receptors and transporters. In addition, the pathological and psychobiological implications related to GABAergic neurotransmission will be considered.