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 (PP125FAK) in rat hippocampal slices by immunoblotting with both antiphosphotyrosine and specific anti-PP125FAK antibodies in the presence of tetrodotoxin (1 microM). Lidocaine induced a concentration-related increase in tyrosine phosphorylation of the 125-kDa band corresponding to PP125FAK phosphorylation (EC50 value=0.39+/-0.09 microM, 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 microM) nor the inhibitor of the ryanodine receptor dantrolene (30 microM). In contrast, it was completely blocked by the protein kinase C (PKC) inhibitors chelerythrin, bisindolylmaleimide I (GF 109203X) and bisindolylmaleimide IX (RO-318220, 10 microM). We conclude that lidocaine increases phosphorylation of the tyrosine kinase PP125FAK in the rat hippocampus by a tetrotoxin (TTX)-insensitive mechanism which involves activation of PKC.
Dahmani
Souhayl
S
Institut National de la Santé et de la Recherche Médicale (INSERM) E 9935, Hôpital Robert Debré, 40 Bd Sérurier, 75019 Paris, France.
Reynaud
Catherine
C
Tesnière
Antoine
A
Rouelle
Danielle
D
Desmonts
Jean-Marie
JM
Mantz
Jean
J
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D019837:Ryanodine Receptor Calcium Release Channel; D014443:Tyrosine; D013779:Tetrodotoxin; D008012:Lidocaine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D011493:Protein Kinase C