Lidocaine increases phosphorylation of focal adhesion kinase in rat hippocampal slices

We examined the effect of lidocaine on phosphorylation of the tyrosine kinase focal adhesion kinase (pp(125)FAK) in rat hippocampal slices by immunoblotting with both antiphosphotyrosine and specific anti-PP(125)FAK antibodies in the presence of tetrodotoxin (1 muM). Lidocaine induced a concentration-related increase in tyrosine phosphorylation of the 125-kDa band corresponding to pp(125)FAK phosphorylation (EC50 value = 0.39 +/- 0.09 muM, maximal effect = 169 +/- 28% of control, P < 0.001). This effect was sensitive to neither the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK 801, 10 muM) nor the inhibitor of the ryanodine receptor dantrolene (30 muM). In contrast, it was completely blocked by the protein kinase C (PKC) inhibitors chelerythrin, bisindolylmaleimide I (GF 109203X) and bisindolylmaleimide IX (RO-318220, 10 muM). We conclude that lidocaine increases phosphorylation of the tyrosine kinase pp(125)FAK in the rat hippocampus by a tetrotoxin (TTX)-insensitive mechanism which involves activation of PKC. (C) 2004 Elsevier B.V. All rights reserved.