PKCζ-Mitogen-activated protein kinase signaling mediates crotalphine-Induced antinociception / A sinalização da proteína quinase ativada por PKCζ-mitógeno medeia a antinocicepção induzida por crotalfina
Toxins, v. 13, n. 12, 912, dez. 2021
Article
em En
| SES-SP, SESSP-IBPROD, SES-SP
| ID: bud-4083
Biblioteca responsável:
BR78.1
ABSTRACT
Crotalphine (CRP) is a structural analogue to a peptide that was first identified in the crude venom from the South American rattlesnake Crotalus durissus terrificus. This peptide induces a potent and long-lasting antinociceptive effect that is mediated by the activation of peripheral opioid receptors. The opioid receptor activation regulates a variety of intracellular signaling, including the mitogen-activated protein kinase (MAPK) pathway. Using primary cultures of sensory neurons, it was demonstrated that crotalphine increases the level of activated ERK1/2 and JNK-MAPKs and this increase is dependent on the activation of protein kinase Cζ (PKCζ). However, whether PKCζ-MAPK signaling is critical for crotalphine-induced antinociception is unknown. Here, we biochemically demonstrated that the systemic crotalphine activates ERK1/2 and JNK and decreases the phosphorylation of p38 in the lumbar spinal cord. The in vivo pharmacological inhibition of spinal ERK1/2 and JNK, but not of p38, blocks the antinociceptive effect of crotalphine. Of interest, the administration of a PKCζ pseudosubstrate (PKCζ inhibitor) prevents crotalphine-induced ERK activation in the spinal cord, followed by the abolishment of crotalphine-induced analgesia. Together, our results demonstrate that the PKCζ-ERK signaling pathway is involved in crotalphine-induced analgesia. Our study opens a perspective for the PKCζ-MAPK axis as a target for pain control.
Texto completo:
1
Coleções:
06-national
/
BR
Base de dados:
SES-SP
/
SESSP-IBPROD
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article