Fontaine B, Klarsfeld A, Changeux J P
Unité de Neurobiologie Moléculaire, Institut Pasteur, Paris, France.
J Cell Biol. 1987 Sep;105(3):1337-42. doi: 10.1083/jcb.105.3.1337.
In cultured chicken myotubes, calcitonin gene-related peptide (CGRP), a peptide present in spinal cord motoneurons, increased by 1.5-fold the number of surface acetylcholine receptors (AChRs) and by threefold AChR alpha-subunit mRNA level without affecting the level of muscular alpha-actin mRNA. Cholera toxin (CT), an activator of adenylate cyclase, produced a similar effect, which did not add up with that of CGRP. In contrast, tetrodotoxin, a blocker of voltage-sensitive Na+ channels, elevated the level of AChR alpha-subunit mRNA on top of the increase caused by either CGRP or CT. 12-O-Tetradecanoyl phorbol-13-acetate (TPA), an activator of protein kinase C, markedly decreased the cell surface and total content of [125I]alpha BGT-binding sites and reduced the rate of appearance of AChR at the surface of the myotubes without reducing the level of AChR alpha-subunit mRNA. Moreover, TPA inhibited the increase of AChR alpha-subunit mRNA caused by tetrodotoxin without affecting that produced by CGRP or CT. Under the same conditions, TPA decreased the level of muscular alpha-actin mRNA and increased that of nonmuscular beta- and gamma-actins mRNA. These data suggest that distinct second messengers are involved in the regulation of AChR biosynthesis by CGRP and muscle activity and that these two pathways may contribute to the development of different patterns of AChR gene expression in junctional and extrajunctional areas of the muscle fiber.
在培养的鸡肌管中，降钙素基因相关肽（CGRP）是一种存在于脊髓运动神经元中的肽，它使表面乙酰胆碱受体（AChR）的数量增加了1.5倍，使AChRα亚基mRNA水平增加了3倍，而不影响肌肉α-肌动蛋白mRNA的水平。霍乱毒素（CT）是一种腺苷酸环化酶激活剂，产生了类似的效果，且与CGRP的效果不叠加。相比之下，河豚毒素是一种电压敏感性Na⁺通道阻滞剂，在CGRP或CT引起的增加基础上，提高了AChRα亚基mRNA的水平。12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）是一种蛋白激酶C激活剂，显著降低了[¹²⁵I]αBGT结合位点的细胞表面水平和总含量，并降低了AChR在肌管表面出现的速率，而不降低AChRα亚基mRNA的水平。此外，TPA抑制了河豚毒素引起的AChRα亚基mRNA的增加，而不影响CGRP或CT产生的增加。在相同条件下，TPA降低了肌肉α-肌动蛋白mRNA的水平，并增加了非肌肉β-和γ-肌动蛋白mRNA的水平。这些数据表明，不同的第二信使参与了CGRP和肌肉活动对AChR生物合成的调节，并且这两条途径可能有助于在肌纤维的接头和接头外区域形成不同模式的AChR基因表达。
