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.
Department of Biology, Faculty of Philosophy, Sciences, and Literature, University of São Paulo, Av. Bandeirantes, 3900-Ribeirão Preto, São Paulo, Brazil, 14040-901.
Renê Oliveira
RO
Beleboni
Renato
R
Guizzo
Andréia Cristina Karklin
AC
Fontana
Andrea Baldocchi
AB
Pizzo
Ruither Oliveira Gomes
RO
Carolino
Leonardo
L
Gobbo-Neto
Norberto Peporine
NP
Lopes
Joaquim
J
Coutinho-Netto
Wagner Ferreira
WF
Dos Santos
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D050485:GABA Plasma Membrane Transport Proteins / Q000187:drug effects; D058786:GABA-B Receptor Agonists; D005901:Glaucoma / Q000517:prevention & control; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D011913:Rats, Inbred BB; D012160:Retina / Q000187:drug effects; D013111:Spider Venoms / Q000737:chemistry*; D013112:Spiders / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C511624:2-amino-5-ureidopentanamide; D050485:GABA Plasma Membrane Transport Proteins; D058786:GABA-B Receptor Agonists; D050487:Glycine Plasma Membrane Transport Proteins; D007473:Ion Channels; D018696:Neuroprotective Agents; D013111:Spider Venoms; D005680:gamma-Aminobutyric Acid; D014508:Urea; D005998:Glycine