Illes P, Zieglgänsberger W, Herz A
Brain Res. 1980 Jun 9;191(2):511-22. doi: 10.1016/0006-8993(80)91299-8.
In the mouse vas deferens, the amplitude of excitatory junction potentials (e.j.p.s.) recorded intracellularly from smooth muscle cells was found to be proportional to stimulus intensity. Normorphine (0.4-2-10 microM) reduced the amplitude of these postsynaptic transients and shifted the stimulus-response curve to the right; i.e. in its presence, higher stimulus intensities were required to elicit an e.j.p. of a similar size to one generated in its absence. Naloxone (0.4 microM) reversed the inhibitory effect of normophine (2 microM). Membrane potentials were unaffected by the concentrations of normorphine employed in solutions of varying ionic compositions. Manoeuvres designed to increase intracellular free calcium, that is increasing the extracellular Ca+ ion concentration (from 2.5 to 5 or 10 mM), removing Mg2+ ions from a medium containing 5 mM Ca2+ or applying 4-aminopyridine (100 microM), enhanced the e.j.p. amplitude and reversed the inhibitory effect of normorphine. Lowering the concentration of Ca2+ ions (from 2.5 to 1 mM) or increasing the concentration of Mg2+ ions (from 1.2 to 4.8 mM) in the bathing solution reduced the amplitude of e.j.p.s. Short trains of impulses (3Hz) facilitated the amplitude of successive e.j.p.s., probably by elevating the intracellular Ca2+ ion concentration. The inhibitory effect of normorphine upon these transients was inversely proportional to the length of the train. It is concluded that the reversal of the effect of normorphine by calcium does not occur at the level of the opiate receptor, and that the opiate depresses the stimulated release of the excitatory transmitter by a reduction in the supply of Ca2+ ions to the stimulus-release coupling mechanism in the sympathetic nerve terminals.
在小鼠输精管中，从平滑肌细胞细胞内记录到的兴奋性接头电位（e.j.p.s.）的幅度被发现与刺激强度成正比。去甲吗啡（0.4 - 2 - 10微摩尔）降低了这些突触后瞬变的幅度，并使刺激 - 反应曲线向右移动；也就是说，在其存在的情况下，需要更高的刺激强度才能引发与不存在时产生的大小相似的e.j.p.。纳洛酮（0.4微摩尔）逆转了去甲吗啡（2微摩尔）的抑制作用。膜电位不受不同离子组成溶液中所用去甲吗啡浓度的影响。旨在增加细胞内游离钙的操作，即增加细胞外Ca⁺离子浓度（从2.5毫摩尔增加到5或10毫摩尔）、从含有5毫摩尔Ca²⁺的培养基中去除Mg²⁺离子或应用4 - 氨基吡啶（100微摩尔），增强了e.j.p.幅度并逆转了去甲吗啡的抑制作用。降低浴液中Ca²⁺离子浓度（从2.5毫摩尔降低到1毫摩尔）或增加Mg²⁺离子浓度（从1.2毫摩尔增加到4.8毫摩尔）会降低e.j.p.s.的幅度。短脉冲串（3赫兹）促进了连续e.j.p.s.的幅度，可能是通过提高细胞内Ca²⁺离子浓度实现的。去甲吗啡对这些瞬变的抑制作用与脉冲串长度成反比。结论是，钙对去甲吗啡作用的逆转不是在阿片受体水平发生的，并且阿片类药物通过减少向交感神经末梢刺激 - 释放偶联机制供应Ca²⁺离子来抑制兴奋性递质的刺激释放。
