Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively.

However, CNP is mainly expressed in the central nervous system, bone and vasculature (Nishikime et al., 2010 and Tobias, 2011). Classically, the clearance of all NPs is carried out by NPR-C and by the neutral endopeptidase (NEP); both of PI3K signaling pathway these proteins are widely expressed in the kidneys, lungs and vascular walls (Chen and Burnett, 2006). The three mammalian NPs have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Over almost 30 years of research, NPs have been found in mammals, amphibians, reptiles, fish, and in plants. Recently, they have also been found in bacteria (Vink et al., 2010). The first natriuretic peptide isolated from animal venoms was a vasorelaxant peptide. This 38 amino acid residue peptide was isolated from green mamba venom and named dendroaspis natriuretic peptide (DNP). Many natriuretic peptides have subsequently been isolated from snake venoms, including Brazilian snakes, such as Crotalus durissus cascavella ( Evangelista et al., 2008), Bothrops jararaca ( Higuchi et al., 1999), Bothrops 5-FU supplier moojeni ( Menin et al., 2008) and Lachesis muta ( Soares et al., 2005). Many genes encoding C-type natriuretic peptides have also been described ( Harvey,

2006). Scorpion venoms are rich sources of small peptide toxins. However, no natriuretic peptides have been isolated from scorpion venom thus far. However, a new family of peptides, called hypotensins, has been isolated from the venom of the yellow scorpion, Tityus serrulatus. These toxins share a similar amino acid signature with the bradykinin-potentiating peptides (BPPs) found in snake venoms ( Verano-Braga et al., 2008 and Verano-Braga et al., 2010). In snakes, BPPs and CNP are encoded by the same gene ( Assakura et al., 2000). This work describes the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide from scorpion venom. Its effects on the

renal function of rats and the mRNA expression of the natriuretic peptide receptors in the kidneys were also evaluated. T. serrulatus venom was acquired from the Instituto Butantan (São Paulo, Brazil). All salts and reagents were of analytical grade Tau-protein kinase and were obtained from certified suppliers. Crude T. serrulatus venom (35 mg) was dissolved in 1.0 mL of ammonium bicarbonate buffer (1 M, pH 8.0). The solution was centrifuged at 4500 × g for 10 min and the supernatant was filtered with a 0.22 μm PVDF filter membrane. Then, 300 μL of the venom solution was loaded onto a Superdex® Gel Filtration Column Peptide HR10/300 GL coupled in a semi preparative Jasco HPLC system (Easton, MD, USA). This column was equilibrated with ammonium bicarbonate buffer (0.25 M, pH 7.8) for 40 min before sample application.