title: A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake).
abstract: Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalus durissus cascavella venom: Pro-Asn-Leu-Pro-Asn-Tyr-Leu-Gly-Ile-Pro-Pro. Although BPP-Cdc presents the classical sequence IPP in the C-terminus, it has a completely atypical N-terminal sequence, which shows very low homology with all other BPPs isolated to date. The pharmacological effects of BPP-Cdc were compared to BBP9a from Bothrops jararaca and captopril. BPP-Cdc (1 μM) significantly increased BK-induced contractions (BK; 1 μM) on the guinea pig ileum by 267.8% and decreased angiotensin I-induced contractions (AngI; 10 nM) by 62.4% and these effects were not significantly different from those of BPP9a (1 μM) or captopril (200 nM). Experiments with 4-week hypertensive 2K-1C rats show that the vasopressor effect of AngI (10 ng) was decreased by 50 μg BPP-Cdc (69.7%), and this result was similar to that obtained with 50 μg BPP9a (69.8%). However, the action duration of BPP-Cdc (60 min) was 2 times greater than that of BPP-9a (30 min). On the other hand, the hypotensive effect of BK (250 ng) was significantly increased by 176.6% after BPP-Cdc (50 μg) administration, value 2.5 times greater than that obtained with BPP9a administered at the same doses (71.4%). In addition, the duration of the action of BPP-Cdc (120 min) was also at least 4 times greater than that of BPP-9a (30 min). Taken together, these results suggest that BPP-Cdc presents more selective action on arterial blood system than BPP9a. Besides the inhibition of ACE, it may present other mechanisms of action yet to be elucidated.
authors.affiliation: Laboratório de Farmacologia Cardiovascular e Renal, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Lopes
authors.affiliation: Laboratório de Farmacologia Cardiovascular e Renal, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Norberto E G
authors.initials: NE
authors.lastname: Junior
authors.affiliation: Laboratório de Farmacologia Cardiovascular e Renal, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Paula P C
authors.initials: PP
authors.lastname: Costa
authors.affiliation: Laboratório de Farmacologia Cardiovascular e Renal, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Patrícia L
authors.initials: PL
authors.lastname: Martins
authors.affiliation: Laboratório de Farmacologia Cardiovascular e Renal, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Cláudia F
authors.initials: CF
authors.lastname: Santos
authors.affiliation: GENPHARMA LTDA, Fortaleza, Ceará, Brazil; Faculdade de Medicina Christus, Fortaleza, Ceará, Brazil.
authors.forename: Ellaine D F
authors.initials: ED
authors.lastname: Carvalho
authors.affiliation: GENPHARMA LTDA, Fortaleza, Ceará, Brazil; Faculdade de Medicina Christus, Fortaleza, Ceará, Brazil; Laboratório de Toxinologia e Farmacologia Molecular, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Maria D F
authors.initials: MD
authors.lastname: Carvalho
authors.affiliation: Instituto Butantan, São Paulo, Brazil.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Pimenta
authors.affiliation: Laboratório de Toxinologia e Farmacologia Molecular, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Cardi
authors.affiliation: Laboratório de Farmacologia Cardiovascular e Renal, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Manassés C
authors.initials: MC
authors.lastname: Fonteles
authors.affiliation: Laboratório de Farmacologia Cardiovascular e Renal, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Nilberto R F
authors.initials: NR
authors.lastname: Nascimento
authors.affiliation: GENPHARMA LTDA, Fortaleza, Ceará, Brazil; Laboratório de Toxinologia e Farmacologia Molecular, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil. Electronic address: carvalhokris@gmail.com.
authors.forename: Krishnamurti M
authors.initials: KM
authors.lastname: Carvalho
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000819:agonists*; D002851:Chromatography, High Pressure Liquid; D003435:Crotalid Venoms / Q000737:chemistry*; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D017819:Viperidae
chemical_list: D003435:Crotalid Venoms; D010455:Peptides; D001920:Bradykinin
keywords: Angiotensin-converting enzyme; Bradykinin-potentiating peptide; Crotalus durissus cascavella venom; Hypertension