title: Antinociceptive response in transgenic mice expressing rat tonin.
abstract: Angiotensin II (Ang II) may be produced directly from angiotensinogen by tonin. Studies have demonstrated that Ang II and its metabolite Ang-(1-7) produce antinociception in pain animal models. The aim of the present study was to determine whether the transgenic mice that express rat tonin (TGM(rTon)) show altered nociceptive behavior and investigate the possible involvement of angiotensin metabolites. Nociception was evaluated using the thermal tail-flick and chemical acetic acid writhing tests, and the drugs were administered by intracerebroventricular and subcutaneous pathways, respectively. Probabilities less than 5% (P<0.05) were considered to be statistically significant (t test; ANOVA/Bonferroni's test). The results demonstrate that the transgenic mice showed an antinociceptive effect in the tail-flick and acetic acid writhing tests. In addition, it was observed that losartan, an AT₁ receptor antagonist and A-779 (D-Ala7-Ang-(1-7)), a Mas receptor antagonist attenuated the antinociceptive behavior. Our data suggest that the Ang II produced in TGM(rTon) induces antinociception via the AT₁ receptor, while the Ang-(1-7) produced from Ang II induced antinociception via the Mas receptor.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, CEP: 31.270.100, Belo Horizonte, Brazil.
authors.forename: Daniela da Fonseca
authors.initials: Dda F
authors.lastname: Pacheco
authors.forename: Cinthia Mara da Fonseca
authors.initials: CM
authors.lastname: Pacheco
authors.forename: Mercia de Paula
authors.initials: Mde P
authors.lastname: Lima
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Alexandro de Lima
authors.initials: Ade L
authors.lastname: Souza
authors.forename: Jorge Luiz
authors.initials: JL
authors.lastname: Pesquero
authors.forename: Andrea
authors.initials: A
authors.lastname: Castro Perez
authors.forename: Igor Dimitri Gama
authors.initials: ID
authors.lastname: Duarte
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D059226:Nociceptive Pain / Q000378:metabolism*; D010147:Pain Measurement; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D020840:Tissue Kallikreins / Q000235:genetics / Q000378:metabolism*
chemical_list: C092006:7-Ala-angiotensin (1-7); D047228:Angiotensin II Type 1 Receptor Blockers; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; C117017:tonin; D020840:Tissue Kallikreins; C118790:angiotensin I (1-7); D019808:Losartan