Yamauchi T, Somei K
Department of Oral Physiology, School of Dentistry, Iwate Medical University, Japan.
Methods Find Exp Clin Pharmacol. 1998 Jul-Aug;20(6):479-87. doi: 10.1358/mf.1998.20.6.485711.
Compound action potentials (CAP) in response to orthodromic stimulation of the presynaptic nerve trunk were recorded extracellularly from the bullfrog sympathetic ganglion. Application of lidocaine, tetracaine or dibucaine significantly suppressed the amplitude of CAP. In the presence of phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C, lidocaine suppression was 3.5-fold more potent, but suppressive effects of tetracaine and dibucaine were not potentiated by PDBu. The acetylcholine (ACh)-induced depolarizing response intracellularly recorded from sympathetic ganglion cells was markedly suppressed by PDBu. Thus, activation of protein kinase C augmented the transmitter release by phosphorylating certain proteins involved in the release mechanism at presynaptic nerve terminals, while it suppressed the nicotinic ACh-receptor activity by phosphorylation at the postsynaptic membrane. However, activation of protein kinase C apparently facilitates synaptic transmission because the augmentation of transmitter release was larger than the suppressive effect on the nicotinic receptors. From these results, it seems likely that protein kinase C activation was responsible for the modified action of lidocaine although the mechanism of this effect is unclear.
从牛蛙交感神经节细胞外记录复合动作电位（CAP），以响应突触前神经干的顺向刺激。应用利多卡因、丁卡因或布比卡因可显著抑制CAP的幅度。在蛋白激酶C激活剂佛波醇12,13 - 二丁酸酯（PDBu）存在的情况下，利多卡因的抑制作用增强了3.5倍，但丁卡因和布比卡因的抑制作用未被PDBu增强。从交感神经节细胞内记录的乙酰胆碱（ACh）诱导的去极化反应被PDBu显著抑制。因此，蛋白激酶C的激活通过磷酸化突触前神经末梢释放机制中涉及的某些蛋白质来增强递质释放，同时通过在突触后膜的磷酸化抑制烟碱型ACh受体活性。然而，蛋白激酶C的激活显然促进了突触传递，因为递质释放的增强大于对烟碱型受体的抑制作用。从这些结果来看，尽管这种效应的机制尚不清楚，但蛋白激酶C的激活可能是利多卡因作用改变的原因。
