Anderson P L, Bamburg J R
Dev Neurosci. 1981;4(4):273-90. doi: 10.1159/000112767.
The effects of the tertiary amine local anesthetics, procaine, lidocaine, and tetracaine, on 8-day-old chick embryo dorsal root ganglia cultured in vitro were examined. All three local anesthetics show a sigmoidal dose-response relationship in inhibiting neurite outgrowth in a reversible fashion. The inhibition of growth independent of the concentration of nerve growth factor and the in vitro culturing conditions. Morphological studies of cells treated with these anesthetics show that low dosages of the drugs (2.25x10-3 M lidocaine, 2x10-3 M procaine, 1x10-4 M tetracaine) cause a retraction of the microspikes into the growth cone and the formation of large swelling along the neurite and at the terminus. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) of these regions show that the loss of microspikes in concomitant with the loss of the bundles of microfilaments and much of the microfilament network. The large swellings are filled with an extensive array of smooth endoplasmic reticulum and agranular vesicles of various sizes. The microtubules and neurofilaments within the neurite fiber appear unaffected. Treatment with high dosages (5.0 x 10-3 M lidocaine, 5.0 x 10-3 M procaine, 5 x 10-4 M tetracaine) results in a rapid wilting of the microspikes followed by retraction of the neurite. The inhibiton of neurite outgrowth and the morphological changes induced by local anesthetics on nerves in culture are similar but not identical to those caused by cytochalasin B, Colchicine, and the calcium ionophore A23187.
研究了叔胺类局部麻醉药普鲁卡因、利多卡因和丁卡因对体外培养的8日龄鸡胚背根神经节的影响。所有这三种局部麻醉药在以可逆方式抑制神经突生长方面均呈现S形剂量反应关系。生长抑制与神经生长因子浓度和体外培养条件无关。对用这些麻醉药处理的细胞进行的形态学研究表明，低剂量药物（2.25×10⁻³M利多卡因、2×10⁻³M普鲁卡因、1×10⁻⁴M丁卡因）会导致微刺缩回生长锥，并在神经突和末端形成大的肿胀。对这些区域进行透射电子显微镜（TEM）和扫描电子显微镜（SEM）观察显示，微刺的丧失与微丝束和许多微丝网络的丧失同时发生。大的肿胀中充满了大量各种大小的光滑内质网和无颗粒小泡。神经突纤维内的微管和神经丝似乎未受影响。高剂量处理（5.0×10⁻³M利多卡因、5.0×10⁻³M普鲁卡因、5×10⁻⁴M丁卡因）导致微刺迅速萎蔫，随后神经突缩回。局部麻醉药对培养神经的神经突生长抑制和形态学改变与细胞松弛素B、秋水仙碱和钙离子载体A23187所引起的相似但不完全相同。
