Relationship between dopamine agonist stimulation of inositol phosphate formation and cytidine diphosphate-diacylglycerol accumulation in brain slices.
Relationship between dopamine agonist stimulation of inositol phosphate formation and cytidine diphosphate-diacylglycerol accumulation in brain slices.
复制标题
多巴胺激动剂刺激磷酸肌醇形成与脑切片中二磷酸胞苷-二酰甘油积累之间的关系。
DOI：
10.1016/s0006-8993(98)01076-2
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发表时间：
1999
期刊：
影响因子：
2.9
通讯作者：
Undie,AS
中科院分区：
文献类型：
--
作者：
Undie,AS
Dopamine receptor-coupled stimulation of inositol phosphate formation has been characterized extensively, but little is known about the diacylglycerol arm of this dual-signaling pathway. This study examined several parameters of cytidine diphosphate–diacylglycerol (CDP–DG) accumulation as an index of agonist-stimulated DG formation. Rat brain slices pre-labeled with 5-[3H ]cytidine were incubated with various test agents in the presence of LiCl and accumulated CDP–DG analyzed. Dopamine and SKF38393 significantly and dose-dependently stimulated CDP–DG accumulation. SKF38393 responses were inhibited by neomycin and reversed by myo-inositol or by exclusion of LiCl. Compared to inositol phosphate formation in 2-[3H ]inositol-prelabeled slices, the CDP–DG responses were proportionately greater, while the agonist EC50values were similar between the two assays. The D1-receptor antagonist SCH23390 inhibited SKF38393-mediated responses at 0.1–10 μM concentrations, whereas greater concentrations reversed the inhibition. SKF38393 effects were completely blocked by the DG kinase inhibitor R59022, thus precluding any role for phospholipase-D or de novo phosphatidate synthesis in the dopaminergic response. D609 which inhibits phosphatidylcholine-specific phospholipase-C (PLC), potently inhibited both CDP–DG accumulation and inositol phosphate formation. These findings demonstrate that the selective D1-receptor antagonist SCH23390 is a partial agonist at the D1-like dopamine receptor that couples to phosphoinositide signaling, that dopaminergic facilitation of phosphoinositide signaling is independent of de novo phosphatidate synthesis, and that the widely used enzyme inhibitor, D-609, is probably not selective for phosphatidylcholine-specific PLC in brain slice preparations. The greater sensitivity of the CDP–DG measurement presents this assay as a reliable and possibly superior index of dopamine receptor-coupled PLC activation in intact tissues.
