Isolation, homology modeling and renal effects of a C-type natriuretic peptide from the venom of the Brazilian yellow scorpion (Tityus serrulatus).

Alves, Renata S; Ximenes, Rafael M; Jorge, Antonio R C; Nascimento, Nilberto R F; Martins, René D; Rabello, Marcelo M; Hernandes, Marcelo Z; Toyama, Daniela O; Toyama, Marcos H; Martins, Alice M C; Havt, Alexandre; Monteiro, Helena S A

Alves, Renata S; Ximenes, Rafael M; Jorge, Antonio R C; Nascimento, Nilberto R F; Martins, René D; Rabello, Marcelo M; Hernandes, Marcelo Z; Toyama, Daniela O; Toyama, Marcos H; Martins, Alice M C; Havt, Alexandre; Monteiro, Helena S A.

Afiliación

Alves RS; 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.

Toxicon ; 74: 19-26, 2013 Nov.

Article en En | MEDLINE | ID: mdl-23911732

RESUMEN

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.

Asunto(s)

Riñón/efectos de los fármacos; Péptido Natriurético Tipo-C/aislamiento & purificación; Venenos de Escorpión/aislamiento & purificación; Escorpiones/química; Secuencia de Aminoácidos; Animales; Brasil; GMP Cíclico/genética; GMP Cíclico/metabolismo; Regulación hacia Abajo; Tasa de Filtración Glomerular; Riñón/metabolismo; Masculino; Datos de Secuencia Molecular; Péptido Natriurético Tipo-C/química; ARN Mensajero/genética; ARN Mensajero/metabolismo; Ratas; Ratas Wistar; Receptores del Factor Natriurético Atrial/genética; Receptores del Factor Natriurético Atrial/metabolismo; Venenos de Escorpión/química; Alineación de Secuencia; Regulación hacia Arriba

Palabras clave

Guanylate cyclase C; Kidney perfusion; Natriuretic peptide; Natriuretic peptide receptor; Tityus serrulatus

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Venenos de Escorpión / Escorpiones / Péptido Natriurético Tipo-C / Riñón Tipo de estudio: Prognostic_studies Límite: Animals País/Región como asunto: America do sul / Brasil Idioma: En Revista: Toxicon Año: 2013 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido

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