佛波醇二丁酸酯增强局部麻醉作用。

Phorbol dibutyrate enhances local anaesthetic action.

作者信息

Austin S, McGivern J, Scholfield C N

机构信息

School of Biomedical Science, Queen's University, Belfast.

出版信息

Br J Pharmacol. 1991 Jan;102(1):146-50. doi: 10.1111/j.1476-5381.1991.tb12145.x.

DOI:10.1111/j.1476-5381.1991.tb12145.x

PMID:1675141

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917896/

Abstract

Synaptically-evoked field responses were elicited by stimulation of the lateral olfactory tract of rat olfactory cortex slices maintained in vitro. 2. Various concentrations of lignocaine (5-500 microM) were applied to the solution bathing the slices. These produced dose-dependent depressions of the synaptically-evoked potential over the concentration range 20-500 microM. The responses completely recovered on washing out the lignocaine. Similar depressions were also noted for procaine (100-1000 microM). 3. In the 47 slices tested, application of beta-phorbol 12,13-dibutyrate (1 microM) increased the amplitude of the synaptic response (from 0.99 +/- 0.05 to 1.36 +/- 0.06 mV). beta-Phorbol 13-monbutyrate (1 microM) had no effect. 4. In the presence of phorbol dibutyrate the depressant effect of lignocaine was increased: the EC50 changed from 91 +/- 10 to 24 +/- 2 microM (a mean potency increase of 3.47 +/- 0.14). A similar increase in potency for procaine was observed with phorbol dibutyrate (from 264 +/- 23 to 49 +/- 9 microM: a 5.49 +/- 0.82 increase in potency). If the tissue was pre-equilibrated in a concentration of lignocaine which produced a 60-80% depression, addition of phorbol ester caused a complete abolition of the evoked potential. 5. beta-Phorbol 13-monobutyrate (1 microM) had no effect on the potency of lignocaine. 6. The Na and K currents generating the action potential in the presynaptic nerve terminals were unaffected by phorbol dibutyrate. The depressant effect of lignocaine on these currents was not modified by phorbol dibutyrate. The depressant effect of lignocaine on these currents was not modified by phorbol dibutyrate. 7. The potentiation of lignocaine could not be accounted for by membrane depolarization or by nonspecific actions of phorbol dibutyrate, and was distinct from the action on transmitter release. Therefore, it seems likely that protein kinase C activation was responsible for the modified action of lignocaine, although the mechanism for this is unclear.

摘要

通过刺激体外培养的大鼠嗅皮质切片的外侧嗅束诱发突触诱发场反应。2. 将不同浓度的利多卡因（5 - 500微摩尔）加入到浸泡切片的溶液中。在20 - 500微摩尔的浓度范围内，这些药物对突触诱发电位产生剂量依赖性的抑制作用。洗去利多卡因后，反应完全恢复。对普鲁卡因（100 - 1000微摩尔）也观察到类似的抑制作用。3. 在测试的47个切片中，应用佛波醇12,13 - 二丁酸酯（1微摩尔）可增加突触反应的幅度（从0.99±0.05毫伏增加到1.36±0.06毫伏）。佛波醇13 - 单丁酸酯（1微摩尔）无此作用。4. 在存在佛波醇二丁酸酯的情况下，利多卡因的抑制作用增强：半数有效浓度（EC50）从91±10微摩尔变为24±2微摩尔（平均效能增加3.47±0.14）。观察到佛波醇二丁酸酯对普鲁卡因的效能也有类似增加（从264±23微摩尔变为49±9微摩尔：效能增加5.49±0.82）。如果组织预先在能产生60 - 80%抑制作用的利多卡因浓度中平衡，加入佛波醇酯会导致诱发电位完全消失。5. 佛波醇13 - 单丁酸酯（1微摩尔）对利多卡因的效能无影响。6. 突触前神经末梢中产生动作电位的钠和钾电流不受佛波醇二丁酸酯影响。佛波醇二丁酸酯不改变利多卡因对这些电流的抑制作用。佛波醇二丁酸酯不改变利多卡因对这些电流的抑制作用。7. 利多卡因的增强作用不能用膜去极化或佛波醇二丁酸酯的非特异性作用来解释，且与对递质释放的作用不同。因此，虽然其机制尚不清楚，但蛋白激酶C激活似乎是利多卡因作用改变的原因。