Structure-function studies of Tityus serrulatus Hypotensin-I (TsHpt-I): A new agonist of B(2) kinin receptor.
In order to better understand the relationship between the primary structure of TsHpt-I - a bradykinin-potentiating peptide (BPP) isolated from the venom of the yellow scorpion Tityus serrulatus, with a non-canonical Lys residue prior to the conservative Pro-Pro doublet - and its cardiovascular effects, a series of ladder peptides were synthesized using the C-terminal portion of TsHpt-I as a template. All synthetic peptides having the Pro-Pro doublet at their C-terminal were able to potentiate the hypotensive effect of bradykinin. Conversely, only those analogues having Lys residue could induce a transient hypotension when intravenously administrated in male rats, indicating that the positive charge located toward the radical of this amino acid residue is crucial for this cardiovascular effect. Differently from all known BPPs, TsHpt-I acts as an agonist of the B(2) receptor and does not inhibit angiotensin-converting enzyme. The capacity of this peptide to activate this subtype of kinin receptor, releasing NO, was also affected by the absence of Lys' side-chain positive charge. Moreover, this study has demonstrated that the minimization of the primary structure of TsHpt-I does not significantly alter the biological effects of this native peptide, which could be of interest for biotechnological purposes.
Verano-Braga
Thiago
T
Laboratório de Venenos e Toxinas Animais, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
Figueiredo-Rezende
Flávia
F
Melo
Marcella N
MN
Lautner
Roberto Q
RQ
Gomes
Enéas R M
ER
Mata-Machado
Leonor T
LT
Murari
Antonela
A
Rocha-Resende
Cibele
C
Elena de Lima
Maria
M
Guatimosim
Sílvia
S
Santos
Robson A S
RA
Pimenta
Adriano M C
AM
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D007022:Hypotension / Q000139:chemically induced; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000819:agonists*; D012604:Scorpion Venoms / Q000737:chemistry*; D020539:Sequence Analysis, Protein; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D043782:Receptor, Bradykinin B2; D012604:Scorpion Venoms; C006791:bradykinin potentiating factors; D009569:Nitric Oxide; D001920:Bradykinin