de Blas A, Adler M, Shih M, Chiang P K, Cantoni G L, Nirenberg M
Proc Natl Acad Sci U S A. 1984 Jul;81(14):4353-7. doi: 10.1073/pnas.81.14.4353.
The effects of putative transmethylation inhibitors were tested on stimulus-secretion coupling and neurotransmitter secretion at synapses between neuroblastoma X glioma hybrid cells and myotubes. 5'-Deoxy-5'-isobutylthio-3-deazaadenosine or 5'-deoxy-5'-isobutylthioadenosine inhibited CDP-choline synthesis catalyzed by cholinephosphate cytidylyltransferase (CTP:cholinephosphate cytidylyltransferase, EC 2.7.7.15) and thereby decreased the rate of phosphatidylcholine synthesis from CDP-choline, but did not affect the transmethylation pathway for phosphatidylcholine synthesis. These compounds also inhibited 45Ca2+ uptake by hybrid cells mediated by voltage-sensitive Ca2+ channels, acetylcholine secretion at synapses, and signal transduction through cell membranes mediated by myotube nicotinic acetylcholine receptors. In contrast, 3-deazaadenosine or adenosine inhibited the transmethylation pathway for phosphatidylcholine synthesis, but had no effect on Ca2+ action potentials, acetylcholine secretion, or signal transduction through cell membranes mediated by nicotinic acetylcholine receptors. These results show that the stimulus-secretion coupling and secretion reactions studied are not dependent on phospholipid methylation and suggest that the activity of action potential Ca2+ channels and the rate of neurotransmitter secretion are functionally coupled to the rate of phosphatidylcholine synthesis via the CDP-choline pathway.
在神经母细胞瘤X胶质瘤杂交细胞与肌管之间的突触处，测试了假定的转甲基化抑制剂对刺激-分泌偶联和神经递质分泌的影响。5'-脱氧-5'-异丁硫基-3-脱氮腺苷或5'-脱氧-5'-异丁硫基腺苷抑制了由胆碱磷酸胞苷转移酶（CTP：胆碱磷酸胞苷转移酶，EC 2.7.7.15）催化的CDP-胆碱合成，从而降低了由CDP-胆碱合成磷脂酰胆碱的速率，但不影响磷脂酰胆碱合成的转甲基化途径。这些化合物还抑制了电压敏感性Ca2+通道介导的杂交细胞对45Ca2+的摄取、突触处的乙酰胆碱分泌以及肌管烟碱型乙酰胆碱受体介导的跨细胞膜信号转导。相比之下，3-脱氮腺苷或腺苷抑制了磷脂酰胆碱合成的转甲基化途径，但对Ca2+动作电位、乙酰胆碱分泌或烟碱型乙酰胆碱受体介导的跨细胞膜信号转导没有影响。这些结果表明，所研究的刺激-分泌偶联和分泌反应不依赖于磷脂甲基化，并提示动作电位Ca2+通道的活性以及神经递质分泌速率通过CDP-胆碱途径在功能上与磷脂酰胆碱合成速率相关联。
