Agmatine inhibits formalin-induced protein kinase C gamma,phosphorylated cAMP response element binding protein,c-Fos and c-Jun up-regulation in the spinal dorsal horn / 中国药理学通报

ABSTRACT

Aim To investigate the changes in the expression of protein kinase C gamma (PKC?), phosphorylated cAMP response element binding protein(pCREB)and immediate-early gene(c-fos and c-jun) in the spinal cord in formalin-induced inflammatory pain and study the effect of agmatine on the changes of PKC? activation, phosphorylation of CREB and expression of c-fos and c-jun.Methods Rats were decapitated at 10, 20 min or 2 h after intraplantar injection of 50 ?l 5% formalin and L_4, 5 spinal cords were dissected. Immunohistochemistry and western blotting analyses were used to observe the expression of PKC?, pCREB, c-fos and c-jun in the spinal dorsal horn and the effect of agmatine on the changes of their expression. Results Unilateral peripheral inflammation induced PKC? activation and CREB phosphorylation bilaterally while c-fos and c-jun expression ipsilaterally in rat spinal cord. PKC activity increased in membrane fractions with unchanged levels in the cytosolic fractions. Pretreatment intraperitoneally with 160 mg?kg-1 agmatine 15 min before inflammation significantly inhibited the activation of PKC? in the membrane fraction, suppressed the phosphorylation of CREB and the expression of c-fos and c-jun. Conclusion The mechanism of the analgesic effect of agmatine may be associated with inhibiting PKC? activation in the plasma membrane, CREB phosphorylation, c-fos and c-jun up-regulation which play roles in the hyperalgesia with peripheral inflammation.