Biochemical and pharmacological studies on a lethal neurotoxic polypeptide fromPhoneutria nigriventer spider venom |
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Authors: | L. R. P. Troncone I. Lebrun F. Magnoli T. Yamane |
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Affiliation: | (1) Lab. Pharmacology, I. BUTANTAN, Av. Vital Brasil 1500, 05503-900 Sao Paulo, SP, Brasil;(2) Lab. Biochemistry, I. Butantan, Av. Vital Brasil 1500, Sao Paulo, SP, Brasil;(3) Lab. Immunochemistry, I. Butantan, Av. Vital Brasil 1500, Sao Paulo, SP, Brasil;(4) Lab. Biotechnology, I. Butantan, Av. Vital Brasil 1500, Sao Paulo, SP, Brasil |
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Abstract: | Fractionation ofPhoneutria nigriventer spider venom by gel filtration and HPLC yielded a few fractions that induced different effects when administered intraperitoneally in mice. One of these fractions, PF3, was chemically characterized as a cysteine-rich polypeptide of 8360 MW. Administered at 0.1 mg/kg, i.p., PF3 induced a progressive paralysis and death of mice within 30 minutes. Partial sequence analysis of PF3 revealed certain homologies with other spider toxins already described, particularly omega-AGAIIA (60%) fromAgelenopsis aperta. Pharmacological characterization carried out in superfused chopped rat striatal tissues preloaded with [3H]-Dopamine ([3H]-DA) showed that PF3 (0.1 g/ml) decreased the [3H]-DA release induced by 20 mM K+ or 100 M glutamate without changing the basal release. At 1 g/ml, PF3 inhibited 33% of the basal release of [3H]-DA; the transmitter release stimulated by K+ or by glutamate was reduced by respectively, 87% and 77% of corresponding control values. PF3 (0.1 g/ml) altered the doseresponse curves of glutamate (1 M–10mM), by reducing by 36% of its maximal effect. Naloxone (1 M) did not influence the effect of PF3. The results indicate that PF3 inhibits the [3H]-DA release induced by membrane depolarization or that mediated by NMDA glutamate receptors. These data suggest that the mechanism of action of PF3 may involve a blockade of Ca2+ channels as well as a direct effect on the exocytotic machinery.Financial support of FAPESP—Fundação de Amparo a Pesquisa do Estado de São Paulo. |
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Keywords: | Spider venom neurotoxin dopamine release calcium channels striatum glutamate |
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