Navegando por Autor "Pimenta, Adriano Monteiro de Castro"
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Item Discovery and characterization of Alamandine : a novel component of the Renin-Angiotensin system.(2013) Lautner, Roberto Queiroga; Villela, Daniel Campos; Silva, Rodrigo Araújo Fraga da; Silva, Neiva Caldeira; Braga, Thiago Verano; Fraga, Fabiana Costa; Jankowski, Joachim; Jankowski, Vera; Sousa, Frederico Barros de; Alzamora, Andréia Carvalho; Soares, Everton Rocha; Barbosa, Claudiane Maria; Kjeldsen, Frank; Oliveira, Aline Cristina; Braga, Janaina Félix; Savergnini, Silvia Silveira Quintão; Etelvino, Gisele Maia; Peluso, Antonio Augusto Bastos; Silva, Danielle Gomes Passos; Ferreira, Anderson José; Alves, Fabiana; Martins, Almir de Sousa; Raizada, Mohan K.; Paula, Renata Dutra de; Santos, Daisy Motta; Klempin, Friederike; Pimenta, Adriano Monteiro de Castro; Alenina, Natalia; Sinisterra Millán, Ruben Dario; Bader, Michael; Santos, Maria José Campagnole dos; Santos, Robson Augusto Souza dosThe renin–angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1–7). To characterize a novel component of the RAS, alamandine. Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1–7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1–7), including vasodilation, antifibrosis, antihypertensive, and central effects. Interestingly, our data reveal that its actions are independent of the known vasodilator receptors of the RAS, Mas, and angiotensin II type 2 receptor. Rather, we demonstrate that alamandine acts through the Mas-related G-protein–coupled receptor, member D. Binding of alamandine to Mas-related G-protein–coupled receptor, member D is blocked by D-Pro7-angiotensin-(1–7), the Mas-related G-protein–coupled receptor, member D ligand β-alanine and PD123319, but not by the Mas antagonist A-779. In addition, oral administration of an inclusion compound of alamandine/β-hydroxypropyl cyclodextrin produced a long-term antihypertensive effect in spontaneously hypertensive rats and antifibrotic effects in isoproterenol-treated rats. Alamandine had no noticeable proliferative or antiproliferative effect in human tumoral cell lines. The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders.Item Purification, amino-acid sequence and partial characterization of two toxins with anti-insect activity from the venom of the South American scorpion Tityus bahiensis (Buthidae).(2001) Pimenta, Adriano Monteiro de Castro; Eauclaire, Marie France Martin; Rochat, Hervé; Figueiredo, Suely Gomes de; Kalapothakis, Evanguedes; Afonso, Luís Carlos Crocco; Lima, Maria Elena deWe report here the isolation by a two-step chromatographic procedure of two new toxins from the South American scorpion Tityus bahiensis. Their amino-acid sequences and some of their biological features were established. The two toxins have different biological properties. Toxin TbIT-I had almost no activity or pharmacological effects in vertebrate tissues whereas it was lethal to house ¯ies (LD50 80.0 ng/house ¯y). In contrast, Tb2-II was active against both mammals (intracerebroventricular injection of 100 ng/mouse was lethal) and insects (LD50 40.0 ng/house ¯y). The amino-acid sequences of these toxins were established and found to be similar (60±95%) to previously described b-toxins from the Tityus genus. Based on the available comparative information, this study attempts identify possible structure±function relationships that may be responsible for the differences in bioactivity displayed by these toxins.Item Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function.(2008) Nunes, Kenia Pedrosa; Gonçalves, Andrey Christian da Costa; Lanza, Luciana Franco; Côrtes, Steyner de França; Cordeiro, Marta do Nascimento; Michael, Richardson; Pimenta, Adriano Monteiro de Castro; Webb, Robert Clinton; Garcia, Maria Elena de Lima PerezThe venom of the spider Phoneutria nigriventer contains several toxins that have bioactivity in mammals and insects. Accidents involving humans are characterized by various symptoms including penile erection. Here we investigated the action of Tx2-6, a toxin purified from the P. nigriventer spider venom that causes priapism in rats and mice. Erectile function was evaluated through changes in intracavernosal pressure/mean arterial pressure ratio (ICP/MAP) during electrical stimulation of the major pelvic ganglion (MPG) of normotensive and deoxycorticosterone-acetate (DOCA)-salt hypertensive rats. Nitric oxide (NO) release was detected in cavernosum slices with fluorescent dye (DAF-FM) and confocal microscopy. The effect of Tx2-6 was also characterized after intracavernosal injection of a non-selective nitric oxide synthase (NOS) inhibitor, L-NAME. Subcutaneous or intravenous injection of Tx2-6 potentiated the elevation of ICP/MAP induced by ganglionic stimulation. L-NAME inhibited penile erection and treatment with Tx2-6 was unable to reverse this inhibition. Tx2-6 treatment induced a significant increase of NO release in cavernosum tissue. Attenuated erectile function of DOCA-salt hypertensive rats was fully restored after toxin injection. Tx2-6 enhanced erectile function in normotensive and DOCA-salt hypertensive rats, via the NO pathway. Our studies suggest that Tx2-6 could be important for development of new pharmacological agents for treatment of erectile dysfunction.