Crain S M, Crain B, Peterson E R, Hiller J M, Simon E J
Life Sci. 1982 Jul 19;31(3):235-40. doi: 10.1016/0024-3205(82)90583-5.
The depressant effects of morphine (0.1-1 microM) on sensory-evoked dorsal-horn network responses in explants of mouse spinal cord with attached dorsal root ganglia (DRGs) were rapidly restored after addition of 4-aminopyridine (4-AP; 0.1 mM) and major components of these cord responses were stably maintained in the presence of the opiate. Moreover, prior exposure of cord-DRG explants to 0.1 mM 4-AP prevented the depressant effects of 0.1 microM morphine on DRG-evoked dorsal-horn responses, and the effects of 1-10 microM morphine were at least partly antagonized. Increased Ca++ levels (5 microM) attenuated the depression of dorsal horn responses by 1-10 micro M morphine and these effects of Ca++ were greatly enhanced in the presence of 4-AP--in some cultures, concentrations of morphine as high as 100 micro M were strongly antagonized during test periods up to 2 hours. Receptor assays showed that 0.1 mM 4-AP +/- 5 mM Ca++ had no effect on stereospecific opiate binding, indicating that the antagonist actions of these agents in our cultures do not occur at the level of the opiate receptor. The relevance of our in vitro studies of 4-AP antagonism of opiate-depressant effects on sensory-evoked dorsal-horn network responses for analyses of problems in opiate analgesia has been strengthened by a recent report demonstrating that 4-AP does, in fact, reverse morphine analgesia in rats, as determined by tail flick tests.
在含有背根神经节（DRG）的小鼠脊髓外植体中，吗啡（0.1 - 1微摩尔）对感觉诱发的背角网络反应的抑制作用，在加入4 - 氨基吡啶（4 - AP；0.1毫摩尔）后迅速恢复，并且这些脊髓反应的主要成分在存在阿片类药物的情况下能稳定维持。此外，预先将脊髓 - DRG外植体暴露于0.1毫摩尔4 - AP可防止0.1微摩尔吗啡对DRG诱发的背角反应的抑制作用，并且1 - 10微摩尔吗啡的作用至少部分被拮抗。钙离子水平升高（5微摩尔）可减弱1 - 10微摩尔吗啡对背角反应的抑制作用，并且在存在4 - AP的情况下，钙离子的这些作用大大增强——在一些培养物中，在长达2小时的测试期内，高达100微摩尔的吗啡浓度被强烈拮抗。受体分析表明，0.1毫摩尔4 - AP ± 5毫摩尔钙离子对立体特异性阿片类结合无影响，表明这些药物在我们培养物中的拮抗作用并非发生在阿片类受体水平。最近一份报告通过甩尾试验证实4 - AP实际上能逆转大鼠的吗啡镇痛作用，这加强了我们关于4 - AP拮抗阿片类药物对感觉诱发的背角网络反应的抑制作用的体外研究对于分析阿片类镇痛问题的相关性。
