RESUMEN
Bradykinin-potentiating peptides (BPPs) or proline-rich oligopeptides (PROs) isolated from the venom glands of Bothrops jararaca (Bj) were the first natural inhibitors of the angiotensin-converting enzyme (ACE) described. Bj-PRO-5a (Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología
, Bothrops
, Venenos de Crotálidos/farmacología
, Dominios Proteicos Ricos en Prolina/fisiología
, Receptor de Bradiquinina B2/fisiología
, Receptor Muscarínico M1/fisiología
, Vasodilatación/efectos de los fármacos
, Inhibidores de la Enzima Convertidora de Angiotensina/química
, Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación
, Animales
, Células CHO
, Cricetinae
, Cricetulus
, Venenos de Crotálidos/química
, Venenos de Crotálidos/aislamiento & purificación
, Relación Dosis-Respuesta a Droga
, Células HEK293
, Humanos
, Masculino
, Ratones
, Ratones Endogámicos BALB C
, Vasodilatación/fisiología
RESUMEN
Amphibian skin secretions are a source of potential new drugs with medical and biotechnological applications. Rich in peptides produced by holocrine-type serous glands in the integument, these secretions play different roles, either in the regulation of physiological skin functions or in the defense against predators or microorganisms. The aim of the present work was to identify novel peptides with bradykinin-like structure and/or activity present in the skin of Phyllomedusa nordestina. In order to achieve this goal, the crude skin secretion of this frog was pre-fractionated by solid phase extraction and separated by reversed-phase chromatography. The fractions were screened for low-molecular-mass peptides and sequenced by mass spectrometry. It was possible to identify three novel bradykinin-related peptides, namely: KPLWRL-NH2 (Pnor 3), RPLSWLPK (Pnor 5) and VPPKGVSM (Pnor 7) presenting vascular activities as assessed by intravital microscopy. Pnor 3 and Pnor 7 were able to induce vasodilation. On the other hand, Pnor 5 was a potent vasoconstrictor. These effects were reproduced by their synthetic analogues.