Primary structure, behavioral and electroencephalographic effects of an epileptogenic peptide from the sea anemone Bunodosoma cangicum.
The primary structure of cangitoxin (CGX), a 4958 Da peptide from the sea anemone Bunodosoma cangicum, was determined: GVACRCDSDGPTVRGNSLSGTLWLTGGCPSGWHNCRGSGPFIGYCCKK. CGX contains all the 11 residues that are conserved and the 5 that are conservatively substituted within or between the type 1 and type 2 sequences of sea anemone peptides with specific action on voltage-sensitive sodium channels. Furthermore, it also has 6 identities (Asp9, Arg14, Asn16, Leu18, Trp33 and Lys48) and 1 homology (Arg36) in the 8 residues of the pharmacophore of the sea anemone ApB which are essential for interaction with mammalian sodium channels. The intrahippocampal injection of CGX induces several sequential behavioral alterations--episodes of akinesia alternating with facial automatisms and head tremor, salivation, rearing, jumping, barrel-rolling, wet dog shakes and forelimb clonic movements--and the electroencephalography analysis shows that they were followed by important seizure periods that gradually evolved to status epilepticus that lasted 8-12 h, similar to that observed in the acute phase of the pilocarpine model of epilepsy. These results suggest that CGX may be an important tool to develop a new experimental model of status epilepticus which may contribute to understanding the etiology of epilepsy and to test the effects of new antiepileptic drugs.
Cunha
Ricardo B
RB
Centro Brasileiro de Serviços e Pesquisas em Proteínas, Departamento de Biologia Celular, Universidade de Brasília, CEP 70.910-900 Brasília, DF, Brazil.
Santana
Alfredo N C
AN
Amaral
Patrícia C
PC
Carvalho
Maria D F
MD
Carvalho
Doris M F
DM
Cavalheiro
Esper A
EA
Maigret
Bernard
B
Ricart
Carlos A O
CA
Cardi
Bruno A
BA
Sousa
Marcelo V
MV
Carvalho
Krishnamurti M
KM
D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003064:Cnidarian Venoms / Q000737:chemistry* / Q000633:toxicity*; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D012615:Sea Anemones; D012640:Seizures / Q000139:chemically induced*; D017386:Sequence Homology, Amino Acid
D003064:Cnidarian Venoms