INOSITOL-RELATED LIPIDS AND MUSCARINIC CNS ACTIONS

越来越明显的是，受刺激的标签 磷脂酸盐(PA)和磷脂酰肌醇(PI) 毒扁豆碱配基到各种组织，是脂质代谢的一种反映 受体与配体的相互作用引发肌醇解体， 尤其是磷脂酰肌醇4，5二磷酸(PIP2)。肌醇 三磷酸(IP3)是PIP2裂解的产物，已被认为是一种 第二个信使。我们的实验室对中枢神经系统特别感兴趣 神经末梢(突触体)中的M受体。我们选择了作为 辅助建立小鼠神经母细胞瘤细胞(克隆N1E-115)和 禽类盐腺(鸭)，因为像神经末梢一样，细胞 不要进行排泄性分泌。除了以下优点外， 研究看似共享共同机制的完整细胞，有 在这些细胞中与脂质变化相关的有用的技术特性 与受体-配基的反应将很容易与 胞吐分泌物对脂类代谢的更大影响 在大多数其他型号中都可以看到。关联的感兴趣的参数 细胞内反应包括细胞周期蛋白、GMP和钙离子的变化。在……里面 此外，我们希望重建一种破碎的细胞制剂，其中 受体-配体的相互作用将直接影响一种 磷脂酶C型磷酸二酯酶将PIP2分解为IP3和 甘油二酯。先前提出的PIP2裂解产生1，2-环 IP3衍生物(CIP3)将被重新调查，因为它可能 信使功能。这些实验具有相关性，不仅在于 它们可能构成一种新颖的第二信使系统，但也可能 解释Li+在情感障碍中的治疗作用 已知Li+的浓度会影响细胞内的分解 肌醇一磷酸脂降解产生的一磷酸肌醇。

It has become increasingly apparent that the stimulated labeling of phosphatidate (PA) and phosphatidylinositol (PI), upon addition of muscarinic ligands to various tissues, is a reflection of lipid turnover in which the receptor-ligand interaction initiates the breakdown of inositide, especially of phosphatidylinositol 4,5 bisphosphate (PIP2). Inositol trisphosphate (IP3), the product of PIP2 cleavage, has been implicated as a second messenger. Our laboratory is particularly interested in the CNS muscarinic receptor in nerve endings (synaptosomes). We have chosen as auxiliary models the murine neuroblastoma cell (clone N1E-115) and the avian salt gland (duck), since like the nerve ending preparation, the cells do not engage in exocytotic secretion. In addition to the advantages of studying intact cells which seemingly share a common mechanism, there is the useful technical property that in these cells lipid changes associated with the receptor-ligand response will easily be distinguished from the more gross effects seen in lipid metabolism following exocytotic secretion seen in most other models. Parameters of interest associated with the intracellular response include changes in cyclin GMP and Ca2+. In addition, we hope to reconstruct a broken cell preparation in which the receptor-ligand interaction will directly affect the action of a phospholipase C-type phosphodiesterase which breaks down PIP2 to IP3 and diacylglycerol. A prior suggestion that PIP2 cleavage yields a 1,2-cyclic IP3 derivative (cIP3) will be reinvestigated in view of its possible messenger function. These experiments have relevance, not only in that they may constitute a novel second messenger system, but also that they may explain the therapeutic role of Li+ in affective disorders, since low concentrations of Li+ are known to affect the breakdown of intracellular inositol monophosphate produced from the degradation of the inositol lipids.