The crude extract from the sea anemone, Bunodosoma caissarum elicits convulsions in mice: possible involvement of the glutamatergic system.
The crude extract from the sea anemone, Bunodosoma caissarum caused dose-dependent convulsions by i.c.v. route in mice. The involvement of the glutamatergic system in the convulsions was investigated. MK-801 and ketamine, non-competitive NMDA receptor antagonists, prolonged the latencies for convulsion onset. AP-5, a competitive NMDA receptor antagonist, reduced the number of animals convulsing and also increased the latency for convulsion onset. 7-Chlorokynurenic acid, an antagonist of the glycine site on the NMDA receptor, reduced the incidence of convulsions. GMP, a nucleotide known to antagonize some NMDA actions, reduced the incidence and the severity of convulsions and prolonged the latency for their onset. Riluzole, a neuroprotective and anticonvulsant agent, blocked the appearance of convulsions. In vitro, the crude extract inhibited [3H]glutamate binding to cerebral cortical membranes and enhanced [3H]glutamate release from cortical synaptosomes. Heating the crude extract to 100 degrees C for 30 min or preincubating it with sphingomyelin, abolished its effect on glutamate release, but did not alter its ability to induce convulsions and to inhibit glutamate binding. However, the convulsant action was inhibited when the crude extract was submitted to trypsin treatment. Our data suggest that the convulsions elicited by the crude extract are not due to the presence of cytolysin and are not related to an increase in glutamate release, but seem to be dependent on the interaction between a peptide component of the extract and NMDA receptors.
Gondran
Margarete
M
Departamento de Bioquímica, CCB, Universidade Federal de Santa Catarina, 88040-900Florianópolis, SC, Brazil.
Eckeli
Alan L
AL
Migues
Paola V
PV
Gabilan
Nelson H
NH
Rodrigues
Ana Lúcia S
AL
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003064:Cnidarian Venoms / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D007649:Ketamine / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate; D012615:Sea Anemones / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D003064:Cnidarian Venoms; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007649:Ketamine; D016291:Dizocilpine Maleate; D014357:Trypsin