Canonico P L, Nicoletti F, Sortino M A, Aleppo G, Scapagnini U
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Funct Neurol. 1992 Jul-Aug;7(4):275-81.
Repeated addition of CDP-choline (100 microM, once a day since the 2nd day of maturation in culture) to corticostriatal neurons led to an increased basal hydrolysis of inositol phospholipids, as revealed by an enhanced formation of [3H]inositolmonophosphate ([3H]InsP) in the presence of 10 mM Li+. This increase was prevented by the muscarinic receptor antagonist, atropine, or by tetrodotoxin, but not by other receptor antagonists, such as L-2-amino-4-phosphonobutanoate (L-AP4), prazosin or ketanserin. The increase in inositol phospholipid hydrolysis induced by repeated addition of CDP-choline was obliterated when cultures were incubated in the presence of the muscarinic receptor agonist, carbamylcholine. CDP-choline had no effect on inositol phospholipid hydrolysis in cultured cerebellar neurons, which are devoid of cholinergic cells. The basal hydrolysis of inositol phospholipids was also increased in hippocampal slices prepared from rats repeatedly injected with CDP-choline (200 mg/kg, i.p. for 15 days). As observed in cultured cortico-striatal neurons, this increase was prevented by atropine and was masked in the presence of carabamylcholine. Taken collectively, these data indicate that repeated exposure to exogenous CDP-choline increases polyphosphoinositide turnover, an effect that results from an increased availability of acetylcholine acting on muscarinic receptors.
对皮质纹状体神经元反复添加胞苷二磷酸胆碱（100微摩尔，自培养成熟的第2天起每天一次）会导致肌醇磷脂的基础水解增加，这在10毫摩尔锂离子存在的情况下，通过[3H]肌醇单磷酸（[3H]InsP）生成的增强得以体现。这种增加可被毒蕈碱受体拮抗剂阿托品或河豚毒素阻止，但不能被其他受体拮抗剂阻止，如L-2-氨基-4-膦酰丁酸（L-AP4）、哌唑嗪或酮色林。当培养物在毒蕈碱受体激动剂氨甲酰胆碱存在的情况下孵育时，反复添加胞苷二磷酸胆碱所诱导的肌醇磷脂水解增加被消除。胞苷二磷酸胆碱对缺乏胆碱能细胞的培养小脑神经元中的肌醇磷脂水解没有影响。在反复注射胞苷二磷酸胆碱（200毫克/千克，腹腔注射15天）的大鼠制备的海马切片中，肌醇磷脂的基础水解也增加。正如在培养的皮质纹状体神经元中观察到的那样，这种增加被阿托品阻止，并且在氨甲酰胆碱存在的情况下被掩盖。总体而言，这些数据表明，反复暴露于外源性胞苷二磷酸胆碱会增加多磷酸肌醇的周转，这种效应是由于作用于毒蕈碱受体的乙酰胆碱可用性增加所致。
