Objective: To investigate the changes of the activity of both protein kinase A and C and the mechanisms of antipyretic action of Guizhi decoction.
Method: The fever responses were observed after combination injection of H-89 (a selective inhibitor of PKA) and calphostin C (a selective inhibitor of PKC), and oral pretreatment of Guizhi decoction in fever rats induced by an intra-cerebroventricular (icv) injection of an EP3 agonist, and both PKA and PKC activity in hypothalamus were measured in rats pretreated with Guizhi decoction and vehicle using isotopic tracing assay.
Result: The rise in rat body temperature was inhibited by H-89, Calphostin C, and Guizhi decoction, moreover, pretreatment with Guizhi decoction reduced PKA activity obviously. PKC activity in model rats exhibited a tendency to drop compared with that of control group, Oral administration of Guizhi decoction in large dose inhibited the response significantly, while the low dose of Guzhi decoction has no effect on PKC.
Conclusion: Both PKA and PKC may participate in the mechanism of fever induction by EP3 agonist. The decrease of PKA and PKC may contribute to the antipyretic action of Guizhi decoction, some isoenzyme of PKC may play a role in the fever production.