title: Lidocaine increases phosphorylation of focal adhesion kinase in rat hippocampal slices.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) E 9935, Hôpital Robert Debré, 40 Bd Sérurier, 75019 Paris, France.
authors.forename: Souhayl
authors.initials: S
authors.lastname: Dahmani
authors.forename: Catherine
authors.initials: C
authors.lastname: Reynaud
authors.forename: Antoine
authors.initials: A
authors.lastname: Tesnière
authors.forename: Danielle
authors.initials: D
authors.lastname: Rouelle
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Desmonts
authors.forename: Jean
authors.initials: J
authors.lastname: Mantz
mesh_terms: 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
chemical_list: 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