乙酰胆碱及其类似物对青蛙微小终板电位频率的抑制作用

Depression of miniature endplate potential frequency by acetylcholine and its analogues in frog.

作者信息

Nikolsky E E, Bukharaeva E A, Strunsky E G, Vyskocil F

机构信息

Institute of Physiology, Czechoslovak Academy of Sciences, Prague.

出版信息

Br J Pharmacol. 1991 Dec;104(4):1024-32. doi: 10.1111/j.1476-5381.1991.tb12544.x.

DOI:10.1111/j.1476-5381.1991.tb12544.x

PMID:1667283

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908837/

Abstract

Acetylcholine (ACh), 7.5 x 10(-5) M, and carbachol, 5 x 10(-6) M (CCh) depressed the frequency of miniature endplate potentials (m.e.p.ps) in the frog (Rana temporaria) sartorius neuromuscular junction with active acetylcholinesterase to about 50-55% of the controls. 2. A similar depression was produced by the nicotinic agonists, nicotine, suberyldicholine and tetramethylammonium. 3. The muscarinic agonists, oxotremorine, methylfurmethide and methacholine were without effect on m.e.p.p. frequency. The muscarinic antagonist, atropine and the nicotinic antagonist, (+)-tubocurarine, had no effect on the depression of m.e.p.p. frequency evoked by CCh. 4. The ganglionic blockers, benzhexonium and IEM-1119, were also without effect on the CCh-evoked depression of m.e.p.p. frequency. 5. Pretreatment of muscles with anticholinesterases did not prevent the CCh-induced drop in m.e.p.p. frequency. 6. The effect of CCh was proportionally the same as in the controls in preparations where the m.e.p.p. frequency was changed by elevation of K+ and in the presence of theophylline, noradrenaline, dibutyryl adenosine 3':5'-cyclic monophosphate (db cyclic AMP) and db cyclic GMP. 7. An inhibitor of Na+,K(+)-ATPase, ouabain, 5 x 10(-5) mol l-1, prevented or reversed the depression of m.e.p.p. frequency by CCh. However, the depression was present in a nominally K(+)-free medium. Insulin and adrenaline, which are considered to be Na+,K(+)-ATPase activators, were without effect on depression of m.e.p.p. frequency. 8. The depression of m.e.p.p. frequency by 5 x 10(-6) M CCh was the same at temperatures between 5 and 30 degrees C with a Q10 near to 1.0. When threshold amounts of CCh were used (6 x 10-7 and 3 x 10-7 M), the depression was less at higher temperatures.9. The receptive structures responsible for the CCh (or ACh)-evoked depression of m.e.p.p. frequency differ pharmacologically from muscarinic, nicotinic ganglionic and neuromuscular junction ACh-receptors as well as from the synaptic cholinesterase, in contrast to previous reports (Duncan & Publicover, 1979).The low temperature-dependence points to the possibility that physical rather than biochemical processes are limiting in this presynaptic effect of cholinomimetics.

摘要

乙酰胆碱（ACh），7.5×10⁻⁵ M，以及卡巴胆碱，5×10⁻⁶ M（CCh），使带有活性乙酰胆碱酯酶的青蛙（林蛙）缝匠肌神经肌肉接头处的微小终板电位（m.e.p.ps）频率降低至对照的约50 - 55%。2. 烟碱样激动剂尼古丁、辛二酰胆碱和四甲铵也产生了类似的抑制作用。3. 毒蕈碱样激动剂氧化震颤素、甲基呋索氯铵和乙酰甲胆碱对m.e.p.p.频率无影响。毒蕈碱拮抗剂阿托品和烟碱拮抗剂（+） - 筒箭毒碱，对CCh诱发的m.e.p.p.频率降低无作用。4. 神经节阻滞剂苯己酮和IEM - 1119，对CCh诱发的m.e.p.p.频率降低也无作用。5. 用抗胆碱酯酶预处理肌肉并不能阻止CCh引起的m.e.p.p.频率下降。6. 在通过升高K⁺改变m.e.p.p.频率的制剂中，以及在茶碱、去甲肾上腺素、二丁酰腺苷3':5'-环磷酸（db环AMP）和db环GMP存在的情况下，CCh的作用与对照相比成比例相同。7. Na⁺,K⁺ - ATP酶抑制剂哇巴因，5×10⁻⁵ mol l⁻¹，可预防或逆转CCh对m.e.p.p.频率的抑制。然而，在名义上无K⁺的培养基中仍存在抑制作用。被认为是Na⁺,K⁺ - ATP酶激活剂的胰岛素和肾上腺素，对m.e.p.p.频率的抑制无作用。8. 5×10⁻⁶ M CCh对m.e.p.p.频率的抑制在5至30摄氏度之间相同，Q₁₀接近1.0。当使用阈值量的CCh（6×10⁻⁷和3×10⁻⁷ M）时，在较高温度下抑制作用较小。9. 与先前的报道（邓肯和普布利科弗，1979年）相反，负责CCh（或ACh）诱发的m.e.p.p.频率降低的感受结构在药理学上与毒蕈碱样、烟碱样神经节和神经肌肉接头ACh受体以及突触胆碱酯酶不同。低温依赖性表明在拟胆碱药的这种突触前效应中，限制因素可能是物理过程而非生化过程。