Xu R, Salpeter M M
Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853-2702, USA.
J Cell Physiol. 1995 Oct;165(1):30-9. doi: 10.1002/jcp.1041650105.
Acetylcholine receptors at the neuromuscular junction of innervated vertebrate muscle (called Rs AChRs) have a stable degradation rate (t1/2 approximately 8-12 days) which accelerates after denervation to a half-life of approximately 3 days, but can be restabilized by reinnervation or by cAMP. We examined the mechanism by which cAMP regulates the Rs degradation rate. When dibutyryl cAMP (DB-cAMP) was applied to denervated mouse diaphragms in organ culture, it stabilized the accelerated degradation rate of the Rs. We found that this stabilization is reversible upon removal of the DB-cAMP, is cAMP specific and is mediated by intracellular cAMP. A major observation of this study is that the cAMP-induced stabilization of Rs AChRs is via protein kinase A (PKA), since H89, a PKA inhibitor, blocked the DB-cAMP induced stabilization of Rs, and H85, an analog of H89, which does not inhibit PKA but does inhibit other kinases as efficiently as H89, did not prevent the DB-cAMP-induced stabilization of Rs degradation. These results suggest that the cAMP messenger system via a PKA-dependent pathway could be among the mechanisms whereby the nerve regulates AChR degradation.
在受神经支配的脊椎动物肌肉的神经肌肉接头处的乙酰胆碱受体（称为Rs AChRs）具有稳定的降解速率（半衰期约为8 - 12天），去神经支配后该速率会加快至半衰期约为3天，但可通过重新神经支配或cAMP使其重新稳定。我们研究了cAMP调节Rs降解速率的机制。当将二丁酰cAMP（DB - cAMP）应用于器官培养中的去神经支配的小鼠膈肌时，它稳定了Rs加速的降解速率。我们发现这种稳定在去除DB - cAMP后是可逆的，具有cAMP特异性且由细胞内cAMP介导。这项研究的一个主要观察结果是，cAMP诱导的Rs AChRs稳定是通过蛋白激酶A（PKA）实现的，因为PKA抑制剂H89阻断了DB - cAMP诱导的Rs稳定，而H89的类似物H85虽然不抑制PKA但与H89一样有效地抑制其他激酶，却不能阻止DB - cAMP诱导的Rs降解稳定。这些结果表明，通过PKA依赖性途径的cAMP信使系统可能是神经调节AChR降解的机制之一。
