Sequence and structure-activity relationship of a scorpion venom toxin with nitrergic activity in rabbit corpus cavernosum.
An alpha-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(omega)-nitro-L-arginine methyl ester (100 microM) and the Na+ channel blocker tetrodotoxin (100 nM). Synthetic peptides based on either Ts3 (P1-16, P17-32, P33-48, P49-64, P9-24, P25-40, P41-56, 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.
Teixeira
Cleber E
CE
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas (SP), 13081-970, Brazil. cleber.teixeira@directnet.com.br
Ifa
Demian R
DR
Corso
Gaetano
G
Santagada
Vincenzo
V
Caliendo
Giuseppe
G
Antunes
Edson
E
De Nucci
Gilberto
G
D000595:Amino Acid Sequence; D000818:Animals; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010413:Penis / Q000033:anatomy & histology / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D011817:Rabbits; D012604:Scorpion Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013329:Structure-Activity Relationship
D010455:Peptides; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D009569:Nitric Oxide