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Sequence and structure‐activity relationship of a scorpion venom toxin with nitrergic activity in rabbit corpus cavernosum
Author(s) -
Teixeira Cleber E.,
Ifa Demian R.,
Corsoi Gaetano,
Santagada Vincenzo,
Caliendo Giuseppe,
Antunes Edson,
De Nucci Gilberto
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0635fje
Subject(s) - venom , peptide , chemistry , nitric oxide , scorpion toxin , scorpion venoms , sodium channel , sodium channel blocker , peptide sequence , tetrodotoxin , channel blocker , toxin , pharmacology , biochemistry , scorpion , sodium , biophysics , biology , calcium , organic chemistry , gene
An α‐toxin responsible for nitric oxide (NO) release in rabbit corpus cavernosum (RbCC) was isolated from Tityus serrulatus venom (TSV). The isolated peptide (molecular mass of 7427.66±0.15 Da) was identified as Ts3 after determination of Cys residues, N‐terminal amino acid analysis, and proteolytic peptide mapping. Ts3 (30 nM) markedly relaxed the RbCC; this response was blocked by the NO synthesis inhibitor N ω ‐nitro‐ L ‐arginine methyl ester (100 μM) and the Na + channel blocker tetrodotoxin (100 nM). Synthetic peptides based on either Ts3 (P 1–16 , p 17–32 , p 33–48 , p 49–64 , p 9–24 , p 25–40 , p 41–56 , YGLPDKVPTKT) or Bukatoxin (isolated from Buthus martensi Karsch scorpion venom) sequence (Buka11, Buka11‐B, PDKVP, PDSEP) were assayed. These peptides slightly relaxed the RbCC, and such an effect was independent of Na + channel activation or NO release. Our results indicate that Ts3 exerts nitrergic actions and contributes to the relaxing activity of TSV in RbCC, thus providing a valuable tool to investigate the mechanisms underlying nerve activation in erectile tissues, because NO released from nitrergic fibers plays a key role in the erectile process. Our findings revealed the key importance of the Ts3 structure three‐dimensional conformation maintenance for biological activity, because linear peptide sequences neither presented substantial relaxations nor was this effect related to nitrergic activity.