title: The C-type natriuretic peptide precursor of snake brain contains highly specific inhibitors of the angiotensin-converting enzyme.
abstract: The bradykinin-potentiating peptides from Bothrops jararaca venom are the most potent natural inhibitors of the angiotensin-converting enzyme. The biochemical and biological features of these peptides were crucial to demonstrate the pivotal role of the angiotensin-converting enzyme in blood pressure regulation. In the present study, seven bradykinin-potentiating peptides were identified within the C-type natriuretic peptide precursor cloned from snake brain. The bradykinin-potentiating peptides deduced from the B. jararaca brain precursor are strong in vitro inhibitors of the angiotensin-converting enzyme (nanomolar range), and also potentiate the bradykinin effects in ex vivo and in vivo experiments. Two of these peptides are novel bradykinin-potentiating peptides, one of which displays high specificity toward the N-domain active site of the somatic angiotensin-converting enzyme. In situ hybridization studies revealed the presence of the bradykinin-potentiating peptides precursor mRNAs in distinct regions of the B. jararaca brain, such as the ventromedial hypothalamus, the paraventricular nuclei, the paraventricular organ, and the subcommissural organ. The biochemical and pharmacological properties of the brain bradykinin-potentiating peptides, their presence within the neuroendocrine regulator C-type natriuretic peptide precursor, and their expression in regions of the snake brain correlated to neuroendocrine functions, strongly suggest that these peptides belong to a novel class of endogenous vasoactive peptides.
authors.affiliation: Center for Applied Toxinology--CAT/CEPID, Instituto Butantan, Avenue.Vital Brazil 15600, São Paulo, SP 05530-900, Brazil.
authors.forename: Mirian A F
authors.initials: MA
authors.lastname: Hayashi
authors.forename: Alessandra F
authors.initials: AF
authors.lastname: Murbach
authors.forename: Danielle
authors.initials: D
authors.lastname: Ianzer
authors.forename: Fernanda C V
authors.initials: FC
authors.lastname: Portaro
authors.forename: Benedito C
authors.initials: BC
authors.lastname: Prezoto
authors.forename: Beatriz L
authors.initials: BL
authors.lastname: Fernandes
authors.forename: Paulo F
authors.initials: PF
authors.lastname: Silveira
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Silva
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Pires
authors.forename: Luiz R G
authors.initials: LR
authors.lastname: Britto
authors.forename: Vincent
authors.initials: V
authors.lastname: Dive
authors.forename: Antonio C M
authors.initials: AC
authors.lastname: Camargo
mesh_terms: D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D001794:Blood Pressure / Q000187:drug effects; D017837:Bothrops; D001920:Bradykinin / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D004357:Drug Synergism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D020098:Natriuretic Peptide, C-Type / Q000096:biosynthesis; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D009928:Organ Specificity; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; C474279:bBPP-10c; C006791:bradykinin potentiating factors; D020098:Natriuretic Peptide, C-Type; D001920:Bradykinin