The role of PKA and PKC epsilon pathways in prostaglandin E(2)-mediated hypernociception


Autoria(s): SACHS, D.; VILLARREAL, C. F.; CUNHA, F. Q.; PARADA, C. A.; FERREIRA, S. H.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2009

Resumo

Background and purpose: Protein kinase (PK) A and the epsilon isoform of PKC (PKC epsilon) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKC epsilon to the development of prostaglandin E(2) (PGE(2))-induced mechanical hypernociception. Experimental approach: Prostaglandin E(2)-induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKC epsilon was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws. Key results: Hypernociception induced by PGE(2) (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A-kinase-anchoring protein St-Ht31 inhibitor peptide (AKAPI)], PKC epsilon (PKC epsilon I) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4-L5), activity of PKA increased at 30 min after injection of PGE(2) but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKC epsilon, while the hypernociception induced by paw injection of PKC epsilon agonist was not affected by an inhibitor of PKA (AKAPI). Conclusions and implications: Taken together, these findings are consistent with the suggestion that PKA activates PKC epsilon, which is a novel mechanism of interaction between these kinases during the development of PGE(2)-induced mechanical hypernociception.

CNPq

FAPESP, Brazil

Identificador

BRITISH JOURNAL OF PHARMACOLOGY, v.156, n.5, p.826-834, 2009

0007-1188

http://producao.usp.br/handle/BDPI/24197

10.1111/j.1476-5381.2008.00093.x

http://dx.doi.org/10.1111/j.1476-5381.2008.00093.x

Idioma(s)

eng

Publicador

WILEY-BLACKWELL PUBLISHING, INC

Relação

British Journal of Pharmacology

Direitos

restrictedAccess

Copyright WILEY-BLACKWELL PUBLISHING, INC

Palavras-Chave #PKA #PKC #cAMP #PGE(2) and rat mechanical hypernociception #PROTEIN-KINASE-C #ROOT GANGLION NEURONS #2ND MESSENGER SYSTEM #RAT SENSORY NEURONS #ASPIRIN-LIKE DRUGS #INFLAMMATORY HYPERALGESIA #MECHANICAL HYPERALGESIA #IN-VITRO #NOCICEPTOR SENSITIZATION #SYMPATHETIC COMPONENT #Pharmacology & Pharmacy
Tipo

article

original article

publishedVersion