Abstract: AIM: To determine the effects of nicotine treatment on protein kinase A and protein kinase C activities in the rat brain.METHODS: Treated with nicotine, nicotinic receptors were in activated state, subacute desensitized state, acute desensitized state or chronic desensitized state, respectively. PKA and PKC sample were abstained from the rat whole brain. PKA and PKC activities were assayed by transferring phosphorus (³²P) into the biotinylated peptide Neurogranin and Kemptide, the most specific substrate for PKC and PKA substrates. In addition, using GeneChip to analyze the changes in genes expression of PKC and PKA related proteins after chronic treatment with nicotine.RESULTS: There were no differences in activities of PKA and PKC between control rats and nicotine-treated rats when nicotinic receptors were activated, but PKA and PKC activities were decreased when nicotinic receptors were in subactue, acute or chronic desensitized states induced by nicotine. After chronic treated with nicotine, PKC Ⅲ was up-regulated, and there were 9 transcripts no changed, such as PKC α, γ, ζand CREB, CREM, etc.CONCLUSION: The desensitized nicotinic receptors as a result of nicotine administration, can down-regulate the PKA and PKC activities, and induce the adaptation changes in signal transduction system, which might be responsible for the mechanism of nicotine tolerance.

Key words: nicotine, desensitization, PKA, PKC, GeneChip