muta muta snake venom, these synthetic immunogens will allow for therapeutic serum development or for vaccination approaches. This research was supported by Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), the INCTTOX PROGRAM of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/Comité Français d’evaluation de la Cooperation Universitaire avec le Brésil (CAPES/COFECUB-Brazil/France). We thank

Dr. Roscovitine clinical trial J. Scott for the gift of phage libraries and the Núcleo de Estudo de Estrutura e Função de Biomoléculas (Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais Belo Horizonte, Minas Gerais, Brasil) for technical support for mass spectrometry. “
“The kallikrein–kinin system plays an important role in several biological functions, including inflammation and cardiovascular homeostasis [7]. The diverse range of effects elicited by kinins is mediated by activation of G protein-coupled receptors, named B1 and B2. Bradykinin (BK) is the natural agonist of the B2 receptor, and its degradation by carboxypeptidases generates the B1 receptor agonist, des-Arg[9]-BK

[34]. Whereas B2 receptors are constitutively expressed and mediate most of the known effects assigned to kinins, B1 receptors are weakly detectable under physiological AZD6244 mw conditions, but rapidly induced by inflammatory stimuli [7] and [23]. Both B1 and B2 receptors act through Gαq to stimulate phospholipase Cβ followed by phosphoinositide hydrolysis and intracellular free Ca2+ mobilization [19]. The resulting intracellular free Ca2+ is the initial step in the activation of nitric oxide synthase (NOS), which catalyzes oxidation of the terminal guanidine nitrogen of l-arginine to form l-citrulline and nitric oxide (NO) [32]. Three NOS isoforms have been described: neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2),

and endothelial NOS (eNOS or NOS3). The iNOS isoform differs from nNOS and eNOS in that it is fully active in the absence of Ca2+[27]. The NOS isoforms have similar enzymatic mechanisms and require presence of co-factors Sulfite dehydrogenase tetrahydrobiopterin (BH4), nicotinamide-adenine dinucleotide (NADPH), flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) for its proper function [25]. In the vasculature, once formed by NOS, endothelial NO diffuses in to the smooth muscle and activates soluble guanylate cyclase that catalyzes the formation of 3′, 5′-cyclic guanosine monophosphate (cGMP), resulting in smooth muscle relaxation and therefore vasodilation [13]. In the last recent years, the development of genetically engineered mice lacking kinin receptors has allowed a better understanding of the physiological and pathological role of the kallikrein–kinin system in a wide range of biological events [31].