title: Isolation, homology modeling and renal effects of a C-type natriuretic peptide from the venom of the Brazilian yellow scorpion (Tityus serrulatus).
abstract: Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated. Fractionation of Tityus serrulatus venom using chromatographic techniques yielded a peptide with a molecular mass of 2190.64 Da, which exhibited the pattern of disulfide bridges that is characteristic of a C-type NP (TsNP, T. serrulatus Natriuretic Peptide). In the isolated perfused rat kidney assay, treatment with two concentrations of TsNP (0.03 and 0.1 μg/mL) increased the perfusion pressure, glomerular filtration rate and urinary flow. After 60 min of treatment at both concentrations, the percentages of sodium, potassium and chloride transport were decreased, and the urinary cGMP concentration was elevated. Natriuretic peptide receptor-A (NPR-A) mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP, whereas NPR-B, NPR-C and CG-C mRNAs were up regulated at the 0.1 μg/mL concentration. In conclusion, this work describes the isolation and modeling of the first natriuretic peptide isolated from scorpion venom. In addition, examinations of the renal actions of TsNP indicate that its effects may be related to the activation of NPR-B, NPR-C and GC-C.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Rua Cap. Francisco Pedro 1210, 60430-370 Forteleza, CE, Brazil.
authors.forename: Renata S
authors.initials: RS
authors.lastname: Alves
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Ximenes
authors.forename: Antonio R C
authors.initials: AR
authors.lastname: Jorge
authors.forename: Nilberto R F
authors.initials: NR
authors.lastname: Nascimento
authors.forename: René D
authors.initials: RD
authors.lastname: Martins
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Rabello
authors.forename: Marcelo Z
authors.initials: MZ
authors.lastname: Hernandes
authors.forename: Daniela O
authors.initials: DO
authors.lastname: Toyama
authors.forename: Marcos H
authors.initials: MH
authors.lastname: Toyama
authors.forename: Alice M C
authors.initials: AM
authors.lastname: Martins
authors.forename: Alexandre
authors.initials: A
authors.lastname: Havt
authors.forename: Helena S A
authors.initials: HS
authors.lastname: Monteiro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001938:Brazil; D006152:Cyclic GMP / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D020098:Natriuretic Peptide, C-Type / Q000737:chemistry / Q000302:isolation & purification*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D012604:Scorpion Venoms / Q000737:chemistry / Q000302:isolation & purification*; D012605:Scorpions / Q000737:chemistry*; D016415:Sequence Alignment; D015854:Up-Regulation; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D006152:Cyclic GMP; D020098:Natriuretic Peptide, C-Type; D012333:RNA, Messenger; D017461:Receptors, Atrial Natriuretic Factor; D012604:Scorpion Venoms; D000099242:Atrial Natriuretic Factor Receptor B; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C
keywords: Guanylate cyclase C; Kidney perfusion; Natriuretic peptide; Natriuretic peptide receptor; Tityus serrulatus