Kilmer S L, Carlsen R C
Exp Neurol. 1987 Feb;95(2):357-67. doi: 10.1016/0014-4886(87)90144-0.
Our previous investigation indicates that forskolin, a robust activator of adenylate cyclase, promotes sensory nerve regeneration in amphibians. The present study was designed to determine if forskolin had a similar effect in mammals. We also wished to test the hypothesis that cyclic AMP modulates nerve regeneration by comparing the effects of chronically infused forskolin with the effects of infused dibutyryl cyclic AMP, 8-bromo cyclic AMP, and the phosphodiesterase inhibitor, theophylline. Our results indicated that all agents promoted some aspect of regeneration. The two which presumably generated the largest increase in cyclic AMP concentration, forskolin and 8-bromo cyclic AMP, had the most profound effect on axonal elongation. All agents decreased the time to sprout initiation, but theophylline produced the largest decrease and its effect was mimicked by caffeine, a methylxanthine with limited ability to inhibit phosphodiesterase. This suggests that sprout formation may be triggered by an increase in intraaxonal free Ca2+, possibly modulated by cyclic AMP. The role of cyclic AMP in axonal elongation remains to be determined, but may be associated with stimulation of protein synthesis in the nerve cell body.
我们之前的研究表明，毛喉素作为腺苷酸环化酶的强效激活剂，可促进两栖动物的感觉神经再生。本研究旨在确定毛喉素在哺乳动物中是否具有类似作用。我们还希望通过比较长期注入毛喉素与注入二丁酰环磷腺苷、8-溴环磷腺苷以及磷酸二酯酶抑制剂茶碱的效果，来检验环磷酸腺苷调节神经再生的假说。我们的结果表明，所有药剂均能促进再生的某些方面。毛喉素和8-溴环磷腺苷这两种药剂可能使环磷酸腺苷浓度升高最多，对轴突伸长的影响最为显著。所有药剂均缩短了发芽起始时间，但茶碱的缩短幅度最大，且咖啡因（一种抑制磷酸二酯酶能力有限的甲基黄嘌呤）能模拟其效果。这表明发芽形成可能由轴突内游离钙离子的增加触发，可能受环磷酸腺苷调节。环磷酸腺苷在轴突伸长中的作用尚待确定，但可能与刺激神经细胞体内的蛋白质合成有关。
