Angiotensin (1-7) prevents angiotensin II-induced nociceptive behaviour via inhibition of p38 MAPK phosphorylation mediated through spinal Mas receptors in mice.
Eur J Pain
; 18(10): 1471-9, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-24733750
ABSTRACT
BACKGROUND:
We have recently demonstrated that intrathecal (i.t.) administration of angiotensin II (Ang II) induces nociceptive behaviour in mice accompanied by a phosphorylation of p38 mitogen-activated protein kinase (MAPK) mediated through Ang II type 1 (AT1 ) receptors. The N-terminal fragment of Ang II, Ang (1-7), plays a pivotal role in counterbalancing many of the well-established actions induced by Ang II. However, the role of Ang (1-7) in spinal nociceptive transmission remains unclear. Therefore, we examined whether i.t. administration of Ang (1-7) can inhibit the Ang II-induced nociceptive behaviour in mice.METHODS:
In the behavioural experiments, the accumulated response time of nociceptive behaviour consisting of scratching, biting and licking in conscious mice was determined during a 25-min period starting after i.t. injection. The distribution and localization of AT1 or Mas receptors were analysed using a MapAnalyzer and confocal microscope, respectively. Phosphorylation of p38 MAPK in the dorsal spinal cord was measured by Western blotting.RESULTS:
The nociceptive behaviour induced by Ang II was dose-dependently inhibited by the co-administration of Ang (1-7). The inhibitory effect of Ang (1-7) was reversed by the co-administration of A779, a Mas receptor antagonist. Western blot analysis showed that the increase in spinal p38 MAPK phosphorylation following the i.t. administration of Ang II was also inhibited by Ang (1-7), and the Ang (1-7) induced-inhibition was prevented by A779.CONCLUSIONS:
Our data show that the i.t. administration of Ang (1-7) attenuates an Ang II-induced nociceptive behaviour and is accompanied by the inhibition of p38 MAPK phosphorylation mediated through Mas receptors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Medula Espinal
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Comportamento Animal
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Angiotensina I
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Angiotensina II
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Proteínas Proto-Oncogênicas
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Receptores Acoplados a Proteínas G
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Proteínas Quinases p38 Ativadas por Mitógeno
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Dor Nociceptiva
Limite:
Animals
Idioma:
En
Revista:
Eur J Pain
Ano de publicação:
2014
Tipo de documento:
Article