FORSKOLIN ACTIVATION OF ADENYLATE-CYCLASE INVIVO STIMULATES NERVE REGENERATION
FORSKOLIN ACTIVATION OF ADENYLATE-CYCLASE INVIVO STIMULATES NERVE REGENERATION
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DOI：
10.1038/307455a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
CARLSEN, RC
中科院分区：
文献类型：
--
作者：
KILMER, SL;CARLSEN, RC
先前的证据表明，在损伤的周围神经1腺苷酸环化酶活性的增加和重新分布表明，神经元环磷酸腺苷浓度的增加可能在周围神经再生中发挥作用。我们报告了我们的发现，积累腺苷酸环化酶活性被翻译成在再生神经残端的环AMP浓度的两倍增加，与再生神经芽的启动和伸长一致。我们试图放大的作用，环腺苷酸在再生中使用毛喉素，一个强大的激活剂腺苷酸环化酶2，产生额外的增加神经元环腺苷酸原位。与等摩尔（10−5）浓度的异丙肾上腺素相比，毛喉素在体外产生的神经元环AMP升高约为40倍。此外，升高的环AMP浓度持续至少60分钟，在持续存在的毛喉素。每天将Forskolin注射到蛙背淋巴囊中，或通过植入的渗透泵递送Forskolin，在冷冻损伤的坐骨神经中产生持续的感觉神经再生率增加40%。我们的结论是，环磷酸腺苷浓度的增加，大概，激活适当的蛋白激酶刺激创伤后再生神经生长。
The previous demonstration of an increase and redistribution of adenylate cyclase activity in injured peripheral nerve1suggests that an increase in neuronal cyclic AMP concentration could play a role in peripheral nerve regeneration. We report our finding that accumulating adenylate cyclase activity was translated into a twofold increase in cyclic AMP concentration in the regenerating nerve stump, coincident with the initiation and elongation of regenerative nerve sprouts. We sought to magnify the role of cyclic AMP in regeneration by using forskolin, a robust activator of adenylate cyclase2, to produce an additional increase in neuronal cyclic AMPin situ. Forskolinin vitroproduced an approximately 40-fold greater elevation in neuronal cyclic AMP than an equimolar (10−5) concentration of isoprenaline. Moreover, the elevated cyclic AMP concentration persisted for at least 60 min in the continued presence of forskolin. Daily injection of forskolin into the dorsal lymph sac ofRana pipiens, or delivery of forskolin through an implanted osmotic pump produced a sustained 40% increase in the rate of sensory nerve regeneration in freeze-lesioned sciatic nerves. We conclude that an increase in cyclic AMP concentration and, presumably, the activation of appropriate protein kinases stimulates regenerative nerve growth following trauma.