Fontaine B, Klarsfeld A, Laufer R, Hökfelt T, Changeux J P
UA CNRS 041149, Institut Pasteur, Département des Biotechnologies, Paris.
Rev Neurol (Paris). 1989;145(3):194-200.
The Calcitonin-Gene Related Peptide (CGRP), a neuropeptide present in chick spinal cord motoneurons, increases the levels of surface acetylcholine receptor (AChR) and of the AChR alpha-subunit mRNA in cultured chick myotubes. Cholera toxin (CT), an activator of adenylate cyclase, produces a similar effect which does not add up with that of CGRP. Consistent with this observation, CGRP increases the content of cyclic AMP in chick muscle cells in culture. Tetrodotoxin (TTX), a blocker of voltage-sensitive Na+ channels, elevates the levels of AChR and of AChR alpha-subunit mRNA. This effect is additive with that of CGRP or CT. TPA (12-O-tetradecanoyl phorbol-13-acetate), an activator of protein kinase C, decreases the level of AChR but has no effect on the level of AChR alpha-subunit mRNA. Interestingly, TPA inhibits the increase of AChR alpha-subunit mRNA caused by TTX without affecting that produced by CGRP or CT. These data suggest that CGRP, which coexists with acetylcholine in spinal cord motoneurons, could be one of the anterograde factors (or a model of such factor) responsible for the enhanced expression of the genes coding for AChR subunits in subneural nuclei, via the activation of adenylate cyclase. Muscle electrical activity would then inhibit the expression of the same genes in extrajunctional nuclei, via another intracellular pathway.
降钙素基因相关肽（CGRP）是一种存在于鸡脊髓运动神经元中的神经肽，它能提高培养的鸡肌管中表面乙酰胆碱受体（AChR）和AChRα亚基mRNA的水平。霍乱毒素（CT）是一种腺苷酸环化酶激活剂，也产生类似的效果，且与CGRP的效果不叠加。与此观察结果一致，CGRP可提高培养的鸡肌肉细胞中环状AMP的含量。河豚毒素（TTX）是一种电压敏感性Na⁺通道阻滞剂，可提高AChR和AChRα亚基mRNA的水平。这种效果与CGRP或CT的效果是相加的。蛋白激酶C激活剂佛波酯（TPA，12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯）可降低AChR水平，但对AChRα亚基mRNA水平无影响。有趣的是，TPA可抑制TTX引起的AChRα亚基mRNA增加，而不影响CGRP或CT所产生的增加。这些数据表明，与乙酰胆碱共存于脊髓运动神经元中的CGRP，可能是通过激活腺苷酸环化酶，负责神经核中编码AChR亚基的基因增强表达的顺行因子之一（或此类因子的一个模型）。然后，肌肉电活动会通过另一条细胞内途径抑制结外核中相同基因的表达。
