ACYLPOLYAMINE  TOXINS  FROM  NEPHILINAE  SPIDER  VENOMS  AS MODELS FOR THE DEVELOPMENT OF NEUROPHARMACEUTICALS

PALMA, M.S. (1), CESAR-TOGNOLLI, L.M.M.(1), SALAMONI, S.(2), COSTA, J.C.(2)

(1) Lab. Structural Biology & Zoochemistry, CEIS/Dept. Biology, IBRC.UNESP, Rio Claro, SP, Brazil; (2) Lab. Neurosciences, IPB-PUCRS, Porto Alegre, RS, Brazil

The acylpolyamine toxins from Nephilinae spiders have been found to block glutamate excitatory activity. Epilepsy has been studied in vitro, mostly on rat hippocampus, through brain slices techniques. A series of  these toxins have been synthesized by using manual solid phase protocols, following a combinatorial strategy. Structure / Activity Relationship studies have been performed with these toxins in order to  verify the effect of the each different structural moiety on the epileptiform activity induced by magnesium-free medium in rat CA1 hippocampal neurons. Experiments were performed on hippocampus slices of control and pilocarpine-treated Wistar rats, prepared and maintained in vitro. Epileptiform activity was induced through omission of magnesium ion from the artificial cerebrospinal fluid (0-Mg2+ ACSF) superfusate and iontophoretic application of       N-methyl-D-aspartate (NMDA). Intracellular recordings were obtained from CA1 pyramidal neurons both of control and epileptic rats. Passive membrane properties were analyzed before and after perfusion with the 0-Mg2+ ACSF and the application of the toxins. During the ictal-like activity, the acylpolyamines were applied by pressure ejection, abolishing this activity. This effect was completely reversed during the washout period when the slices were formerly perfused with artificial cerebrospinal fluid (ACSF) and again with 0-Mg2+ ACSF. Our results suggest that the acylpolyamine toxins from Nephilinae spider venoms  are potent blockers of the induced epileptiform activity at different levels, according to each different structural moiety under consideration and be used as models of  the development novel neuropharmaceuticals.

KEY-WORDS:  orb-web-spider venom; acylpolyamine toxins; glutamate-receptor blocker;  anti-epileptic action.

FINANCIAL SUPPORT: BIOprospecTA-FAPESP / CNPq