Endothelins induce ETB receptor-mediated mechanical hypernociception in rat hindpaw: roles of cAMP and protein kinase C.
Eur J Pharmacol
; 501(1-3): 87-94, 2004 Oct 06.
Article
em En
| MEDLINE
| ID: mdl-15464066
ABSTRACT
The present study assesses the capacity of endothelins to induce mechanical hypernociception, and characterises the receptors involved and the contribution of cAMP and protein kinases A (PKA) and C (PKC) to this effect. Intraplantar administration of endothelin-1, endothelin-2 or endothelin-3 (3-30 pmol) induced dose- and time-dependent mechanical hypernociception, which was inhibited by BQ-788 (N-cys-2,6-dimethylpiperidinocarbonyl-l-gamma-methylleucyl-d-1-methoxycarboyl-d-norleucine; endothelin ET(B) receptor antagonist), but not BQ-123 (cyclo[d-Trp-d-Asp-Pro-d-Val-Leu]; endothelin ET(A) receptor antagonist; each at 30 pmol). The selective endothelin ET(B) receptor agonist BQ-3020 (N-Ac-Ala(11,15)-endothelin-1 (6-21)) fully mimicked the hypernociceptive effects of the natural endothelins. Treatments with indomethacin, atenolol or dexamethasone did not inhibit endothelin-1-evoked mechanical hypernociception. However, endothelin-1-induced mechanical hypernociception was potentiated by the cAMP phosphodiesterase inhibitor rolipram (4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone) and inhibited by the PKC inhibitors staurosporine and calphostin C, but was unaffected by the PKA inhibitor H89 (N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide). Thus, endothelins, acting through endothelin ET(B) receptors, induce mechanical hypernociception in the rat hindpaw via cAMP formation and activation of the PKC-dependent phosphorylation cascade.
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Base de dados:
MEDLINE
Assunto principal:
Medição da Dor
/
Proteína Quinase C
/
Endotelinas
/
AMP Cíclico
/
Receptor de Endotelina B
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article