Shyng S L, Xu R, Salpeter M M
Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853-2702.
Neuron. 1991 Mar;6(3):469-75. doi: 10.1016/0896-6273(91)90254-w.
We used mouse diaphragm muscle in organ culture to study the stabilization of acetylcholine receptor (AChR) degradation at denervated neuromuscular junctions. After denervation, the degradation rate of the AChRs present prior to denervation (slowly degrading, or Rs, AChRs) accelerates from the predenervation degradation half-life (t1/2) of approximately 8-10 days to a t1/2 of approximately 2-3 days. We report that addition to the organ culture medium of pharmacological agents that elevate cytoplasmic cAMP levels (forskolin, dibutyryl cAMP, and 8-bromo-cAMP) reversed the change in t1/2 caused by denervation, whereas addition of 1,9-dideoxyforskolin, a forskolin analog that does not elevate cytoplasmic cAMP levels, did not reverse the effect of denervation. The degradation rate of AChRs in primary myotube cultures and that of the newly synthesized AChRs in denervated muscle were little affected by forskolin or dibutyryl cAMP. The possibility is raised that the modulation of Rs AChR degradation by innervation may be mediated by cAMP.
我们利用器官培养中的小鼠膈肌来研究去神经支配的神经肌肉接头处乙酰胆碱受体（AChR）降解的稳定性。去神经支配后，去神经支配前存在的AChR（缓慢降解型，或Rs，AChR）的降解速率从去神经支配前约8 - 10天的降解半衰期（t1/2）加速至约2 - 3天的t1/2。我们报告称，向器官培养基中添加可提高细胞质cAMP水平的药理试剂（福斯可林、二丁酰cAMP和8 - 溴 - cAMP）可逆转去神经支配引起的t1/2变化，而添加1,9 - 二脱氧福斯可林（一种不会提高细胞质cAMP水平的福斯可林类似物）则不会逆转去神经支配的效应。福斯可林或二丁酰cAMP对原代肌管培养物中AChR的降解速率以及去神经支配肌肉中新合成的AChR的降解速率影响很小。由此提出一种可能性，即神经支配对Rs AChR降解的调节可能由cAMP介导。
