ANGIOTENSIN III MODULATES the NOCICEPTIVE CONTROL MEDIATED BY the PERIAQUEDUCTAL GRAY MATTER

ANGIOTENSIN III MODULATES the NOCICEPTIVE CONTROL MEDIATED BY the PERIAQUEDUCTAL GRAY MATTER

Author Pelegrini-da-Silva, A. Google Scholar
Rosa, E. Google Scholar
Guethe, L. M. Google Scholar
Juliano, M. A. Autor UNIFESP Google Scholar
Prado, W. A. Google Scholar
Martins, A. R. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Endogenous angiotensin (Ang) II and/or an Ang II-derived peptide, acting on Ang type I (AT(1)) and Ang type 2 (AT(2)) receptors, can carry out part of the nociceptive control modulated by periaqueductal gray matter (PAG). However, neither the identity of this putative Ang-peptide, nor its relationship to Ang II antinociceptive activity was clarified. Therefore, we have used tail-flick and incision allodynia models combined with an HPLC time course of Ang metabolism, to study the Ang III antinociceptive effect in the rat ventrolateral (vi) PAG using peptidase inhibitors and receptor antagonists. Ang III injection into the vIPAG increased tail-flick latency, which was fully blocked by Losartan and CGP 42,112A, but not by divalinal-Ang IV, indicating that. Ang III effect was mediated by AT(1) and AT(2) receptors, but not by the AT(4) receptor. Ang III injected into the vIPAG reduced incision allodynia. Incubation of Ang II with punches of vIPAG homogenate formed Ang III, Ang (1-7) and Ang IV. Amastatin (AM) inhibited the formation of Ang III from Ang II by homogenate, and blocked the antinociceptive activity of Ang II injection into vIPAG, suggesting that aminopeptidase A (APA) formed Ang III from Ang II. Ang III can also be formed from Ang I by a vIPAG alternative pathway. Therefore, the present work shows, for the first time, that: (i) Ang III, acting on AT(1) and AT(2) receptors, can elicit vIPAG-mediated antinociception, (ii) the conversion of Ang II to Ang III in the vIPAG is required to elicit antinociception, and (iii) the antinociceptive activity of endogenous Ang II in vIPAG can be ascribed preponderantly to Ang III. (C) 2009 IBRO. Published by Elsevier B.V. All rights reserved.
Keywords antinociception
tail flick and allodynia models
renin-angiotensin system
Losartan
CGP 42
112A
divalinal-angiotensin IV
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
FAEPA
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2009-12-15
Published in Neuroscience. Oxford: Pergamon-Elsevier B.V., v. 164, n. 3, p. 1263-1273, 2009.
ISSN 0306-4522 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1263-1273
Origin http://dx.doi.org/10.1016/j.neuroscience.2009.09.004
Access rights Closed access
Type Article
Web of Science ID WOS:000271852000035
URI http://repositorio.unifesp.br/handle/11600/32020

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