Joro spider toxin (JSTX-3) and its analogue, 1-Naphtylacetylspermin (NpAc), inhibit glutamate toxicity on mice brain in vivo and in vitro

Hitni, T. and titip, N.

ff~tf; of JO~O spider toxin (JSTX-3) and its analogue

1-naphtylacetylspermine (NpAc) were studied on mamstem. JSTX-3 was isolated from Joro spiders (Nephila cravata) (Aramaki, 1986), and has on the endplate of invertebrates. NpAc is an artificial analogue with ~~s~~on in the crustacea endplate (Asami, 1989). This time, we ts on mice brain, because glutamate is a major excitatory neurotrans~~~ whether JSTX-3 and NpAc has e mitter in mammahan central nervous system. 1) Effects of JSTX-3 and NpAc per se. JSTX-3 was injected into lateral ventricles of chronically cannulated mice (i.c.v. injection), for blood-brain-barrier was prospected to have a low , which are partially consisted of polycationic polyamine part. JSTX-3 induced behavioral such as increase in motor activities (Y 12 nmol/bmin)~ long lasting suppression and ataxia d tremors with ~t~ttent clonic convulsions (400 nmol/bra.in). Almost the same syndromes were induced by NpAc, though the increase of motor activities was lasting longer and the ataxic syndrome was recovered quickly than the case of JSTX-3.2) Antagonizing effect on the convulsions induced by glutamate agonists. L-Glutamate and its analogues., such as kainate (KA), quisqualate (QA) and N-methyl-D-aspartate (NMDA) are potentially excitatory toxic on neurons and induce convulsions when i.c.v. injected. In order to estimate the stung effects of JSTX-3 and NpAc on glutamate agonists, These agonists were i c v. injected and the latencies to the first convulsions and to death were measured as the indicators in the presence and absence of JSTX-3 and NpAc. The results were summarized in Table 1. JSTX-3 distinctly inhibited QA-induced convulsions in both indicators, but showed no effects in either KA- or NMDA- induced convulsions. On the contrary, NpAc rather intensified the KA-induced convulsions, and showed weak inhibitory effect on QA- and NMDA-induced convulsions. 3) strong effect on the glutamate-induced toxicity on cultured neurons. Cultured neurons are damaged when to the excess glutamate or its anafogues. We estimated the neuronal damages in the presence or absence of and NpAc, measuring the leaked lactatedehydrogenase activity as the indicator, The results were summarized in Table 1. JSTX-3 and NpAc reduced QA-induced neuronal damages. Conclusion 1. JSTX-3 inbibits QA neurotoxicity in vivo and in vitro. 2. NpAc inhibits QA neurotoxicity, but it has a low selectivity.

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