Oligopeptidases B from Trypanossoma cruzi and Trypanossoma brucei Inhibit Inflammatory Pain in Mice by Targeting Seroton
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Oligopeptidases B from Trypanossoma cruzi and Trypanossoma brucei Inhibit Inflammatory Pain in Mice by Targeting Serotoninergic Receptors Rafaela Quintanilha Abrahão,1,2 Adriano Cardoso Franciosi,1 Douglas Andrade,2 Luiz Juliano,2 Maria Aparecida Juliano,2 Renata Giorgi,3 and Camila Squarzoni Dale1,4
Abstract—In the present study, the antinociceptive profile of oligopeptidases B from Trypanosoma cruzi (OPTc) and Trypanosoma brucei (OPTb) were examined in mice evaluated by the acetic acidinduced writhing test. Both OPTc and OPTb injected intraperitoneally attenuated the writhing numbers in the acetic acid-induced writhing test. This effect was not dependent on the enzymatic activity, but the enzyme structure was important for this purpose. Intraperitoneal pretreatment with methysergide (5-HT serotonergic receptor antagonist) attenuated antinociceptive effect induced by both OPTc and OPTb in the writhing test. However, naloxone (opioid receptor antagonist) or yohimbine (α2-adrenergic receptor antagonist) did not affect antinociception induced by both oligopeptidases. Our results suggest that OPTc and OPTb show antinociceptive property in the writhing test. Furthermore, this antinociceptive effect may be mediated by serotonergic receptor but not opioidergic or α2-adrenergic receptors. KEY WORDS: oligopeptidases B; Trypanossoma cruzi; Trypanossoma brucei; mice; antinociception; hyperalgesia.
positive bacteria, spirochetes, and protozoans but not in higher eukaryotes with the exception of plants [5–11]. OPB has been reported to be an important virulence factor in some trypanosomatids [12, 13]. In Trypanosoma cruzi, OPB plays a part in the invasion of nonphagocytic cells by trypomastigotes, via triggering an increase in the host cell’s free intracellular calcium [14– 16]. T. cruzi OPB null mutant trypomastigotes are 75 % less infective to mammalian cells than wild-type T. cruzi and exhibited lower parasitemia in mice [16]. Parasite OPB is released into the bloodstream of animals infected with Trypanossoma brucei, apparently through lysis of dying parasites [17–19]. The enzyme is thought to reduce the levels of the regulatory peptide hormone atrial natriuretic factor in the plasma of T. bruceiinfected dogs and of Trypanosoma evansi-infected rats [17, 20], potentially leading to the circulatory system lesions which are observed in the trypanosome infections [12]. Serine oligopeptidases of trypanosomatids are emerging as important virulence factors and therapeutic targets in trypanosome infections. In this sense, it is demonstrated that the trypanocidal drugs pentamidine,
INTRODUCTION Oligopeptidase B (OPB, EC3.4.21.83) belongs to the prolyloligopeptidase (POP) family of serine proteases (clan SC, family S9) [1] and, unlike other POP members, does not cleave after proline residues. However, OPB shares similarities of catalytic domain amino acids and of secondary structure prediction with POP family members [2, 3]. OPB is a processing enzyme, specific for the basic amino acid pairs of peptides [4]. OPB has been described in Gr
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