title: Anxiolytic activity and evaluation of potentially adverse effects of a bradykinin-related peptide isolated from a social wasp venom.
abstract: Anxiety disorders are major health problems in terms of costs stemming from sick leave, disabilities, healthcare and premature mortality. Despite the availability of classic anxiolytics, some anxiety disorders are still resistant to treatment, with higher rates of adverse effects. In this respect, several toxins isolated from arthropod venoms are useful in identifying new compounds to treat neurological disorders, particularly pathological anxiety. Thus, the aims of this study were to identify and characterize an anxiolytic peptide isolated from the venom of the social wasp Polybia paulista. The peptide was identified as Polisteskinin R, with nominal molecular mass [M+H](+)=1301Da and primary structure consisting of Ala-Arg-Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH. The anxiolytic effect was tested using the elevated plus maze test. Moreover, adverse effects on the spontaneous behavior and motor coordination of animals were assessed using the open field and rotarod tests. Polisteskinin R induced a dose-dependent anxiolytic effect. Animals treated with the peptide and diazepam spent significantly more time into the open arms when compared to the groups treated with the vehicle and pentylenetetrazole. No significant differences in spontaneous behavior or motor coordination were observed between the groups, showing that the peptide was well tolerated. The interaction by agonists in both known BK receptors induces a variability of physiological effects; Polisteskinin R can act on these receptors, inducing modulatory activity and thus, attenuating anxiety behaviors. The results of this study demonstrated that the compound Polisteskinin R exerted potent anxiolytic effects and its analogues are promising candidates for experimental pharmacology.
authors.affiliation: Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília, DF, Brazil; Graduate Program of Animal Biology, University of Brasília, Brasília, DF, Brazil.
authors.forename: Lilian Carneiro
authors.initials: LC
authors.lastname: dos Anjos
authors.affiliation: Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília, DF, Brazil; Graduate Program of Animal Biology, University of Brasília, Brasília, DF, Brazil.
authors.forename: Flávia Maria Medeiros
authors.initials: FM
authors.lastname: Gomes
authors.affiliation: Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília, DF, Brazil.
authors.forename: Lucianna Lopes
authors.initials: LL
authors.lastname: do Couto
authors.affiliation: Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília, DF, Brazil.
authors.forename: Cecília Alves
authors.initials: CA
authors.lastname: Mourão
authors.affiliation: Graduate Program of Animal Biology, University of Brasília, Brasília, DF, Brazil.
authors.forename: Karla Graziela
authors.initials: KG
authors.lastname: Moreira
authors.affiliation: Graduate Program of Animal Biology, University of Brasília, Brasília, DF, Brazil; Laboratory of Mass Spectrometry and Laboratory of Nanobiotechnology, Embrapa Genetic Resources and Biotechnology, Brasília, DF, Brazil.
authors.forename: Luciano Paulino
authors.initials: LP
authors.lastname: Silva
authors.affiliation: Neuropharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília, DF, Brazil; Graduate Program of Animal Biology, University of Brasília, Brasília, DF, Brazil. Electronic address: mmortari@unb.br.
authors.forename: Márcia Renata
authors.initials: MR
authors.lastname: Mortari
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D001920:Bradykinin / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D010446:Peptide Fragments / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014862:Wasp Venoms / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*
chemical_list: D014151:Anti-Anxiety Agents; D010446:Peptide Fragments; D014862:Wasp Venoms; D001920:Bradykinin
keywords: Elevated plus maze; Open field; Pathological anxiety; Polisteskinin R; Polybia paulista; Rotarod