Dahmani Souhayl, Reynaud Catherine, Tesnière Antoine, Rouelle Danielle, Desmonts Jean-Marie, Mantz Jean
Institut National de la Santé et de la Recherche Médicale (INSERM) E 9935, Hôpital Robert Debré, 40 Bd Sérurier, 75019 Paris, France.
Eur J Pharmacol. 2004 Apr 5;489(1-2):55-8. doi: 10.1016/j.ejphar.2004.02.012.
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.
我们通过在存在河豚毒素（1微摩尔）的情况下，用抗磷酸酪氨酸抗体和特异性抗PP125FAK抗体进行免疫印迹，研究了利多卡因对大鼠海马切片中酪氨酸激酶粘着斑激酶（PP125FAK）磷酸化的影响。利多卡因导致与PP125FAK磷酸化相对应的125 kDa条带的酪氨酸磷酸化呈浓度依赖性增加（EC50值 = 0.39 ± 0.09微摩尔，最大效应 = 对照的169 ± 28%，P < 0.001）。这种效应既不敏感于N-甲基-D-天冬氨酸（NMDA）受体拮抗剂地佐环平（MK 801，10微摩尔），也不敏感于兰尼碱受体抑制剂丹曲林（30微摩尔）。相反，它被蛋白激酶C（PKC）抑制剂白屈菜红碱、双吲哚马来酰亚胺I（GF 109203X）和双吲哚马来酰亚胺IX（RO-318220，10微摩尔）完全阻断。我们得出结论，利多卡因通过一种不依赖河豚毒素（TTX）的机制增加大鼠海马中酪氨酸激酶PP125FAK的磷酸化，该机制涉及PKC的激活。
