Leeuwin R S, Veldsema-Currie R D, van Wilgenburg H, Ottenhof M
Eur J Pharmacol. 1981 Jan 16;69(2):165-73. doi: 10.1016/0014-2999(81)90411-8.
Dexamethasone (50 microgram/kg) significantly increased the LD50 of d-tubocurarine (d-TC) when administered i.p. simultaneously with d-TC. Choline (50 and 100 mg/kg) gave some protection against the lethal effects of d-TC and the cholinesterase inhibitors neostigmine (250 microgram/kg) and physostigmine (1000 microgram/kg) provided full protection against doses of d-TC twice the LD50. The blocking effect of d-TC (75 microgram/kg) on the sciatic nerve-tibialis anterior muscle preparation was antagonized by dexamethasone. Prednisolone delayed the occurrence of a complete neuromuscular block caused by d-TC in the phrenic nerve-diaphragm preparation, and antagonized the effect of d-TC on short tetanic contractions. d-TC (5 mumol/l) inhibited the [14C]choline uptake in the endplate-rich region of the rat diaphragm during stimulation. This inhibition was antagonized by dexamethasone as well as by physostigmine. The incorporation of radioactive choline into acetylcholine was inhibited in the presence of d-TC (15 mumol/l), and both dexamethasone and physostigmine counteracted this inhibition. It is concluded from these experiments that d-TC very probably has an effect on the choline carrier system. These experimental results support the hypothesis that glucocorticoids may improve reduced muscle performance by direct presynaptic effects at the neuromuscular junction.
当腹腔注射地塞米松（50微克/千克）并同时注射筒箭毒碱（d-TC）时，可显著提高d-TC的半数致死量（LD50）。胆碱（50和100毫克/千克）对d-TC的致死效应有一定的保护作用，而胆碱酯酶抑制剂新斯的明（250微克/千克）和毒扁豆碱（1000微克/千克）可对两倍LD50剂量的d-TC提供完全保护。地塞米松可拮抗d-TC（75微克/千克）对坐骨神经-胫前肌标本的阻断作用。泼尼松龙可延缓膈神经-膈肌标本中由d-TC引起的完全神经肌肉阻滞的发生，并拮抗d-TC对短强直收缩的作用。d-TC（5微摩尔/升）在刺激过程中抑制大鼠膈肌富含终板区域的[14C]胆碱摄取。这种抑制作用可被地塞米松以及毒扁豆碱所拮抗。在d-TC（15微摩尔/升）存在的情况下，放射性胆碱掺入乙酰胆碱的过程受到抑制，而地塞米松和毒扁豆碱均可对抗这种抑制作用。从这些实验可以得出结论，d-TC很可能对胆碱载体系统有影响。这些实验结果支持了糖皮质激素可能通过在神经肌肉接头处的直接突触前效应来改善肌肉功能减退的假说。
