Marinetti G V, Morris T W, Ekholm S E, Leakey P
Department of Biochemistry, University of Rochester Medical Center, New York 14642.
Invest Radiol. 1992 Mar;27(3):224-9. doi: 10.1097/00004424-199203000-00009.
Radiographic contrast media (RCM) used in the subarachnoid space are associated with occasional adverse reactions. This study examines the possibility that RCM reactions are caused by interactions with the plasma membrane phosphatidylinositol (PI) second messenger system. Isolated nerve endings, known as synaptosomes, were produced from rat brain homogenates. The synaptosomes were then incubated with RCM to determine if 32Pi labeling of the PIs or the uptake of 45Ca were influenced in a manner consistent with known mechanisms. The RCM metrizamide, iopamidol, iodixanol, and iotrol (but not iohexol) increased the 32Pi labeling. Hyperosmolality produced large increases in phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4, 5,-bisphosphate (PIP2) labeling. In the non-depolarized state iodixanol, but not metrizamide or iohexol, caused a time-dependent increase in 45Ca uptake. Iodixanol, iohexol, and metrizamide also augmented the veratrine-stimulated uptake of calcium, but none of the RCM affected the uptake of Ca resulting from potassium depolarization. The increased 32Pi labeling of the PIs caused by RCM is not directly related to Ca uptake, because the direction of change is wrong. RCM perturbations of the plasma membrane may cause an inhibition of other membrane components and systems. Hyperosmolality also may cause inhibition of membrane components. It is not known if these effects are important in clinically observed RCM toxicity.
用于蛛网膜下腔的放射造影剂（RCM）偶尔会引发不良反应。本研究探讨了RCM反应是否由与质膜磷脂酰肌醇（PI）第二信使系统的相互作用所引起。从大鼠脑匀浆中制备出被称为突触体的分离神经末梢。然后将突触体与RCM一起孵育，以确定PI的32Pi标记或45Ca的摄取是否以与已知机制一致的方式受到影响。RCM药物甲泛葡胺、碘帕醇、碘克沙醇和碘曲仑（但不是碘海醇）增加了32Pi标记。高渗状态使磷脂酰肌醇-4-磷酸（PIP）和磷脂酰肌醇-4,5-二磷酸（PIP2）标记大幅增加。在非去极化状态下，碘克沙醇而非甲泛葡胺或碘海醇导致45Ca摄取随时间增加。碘克沙醇、碘海醇和甲泛葡胺也增强了藜芦碱刺激的钙摄取，但没有一种RCM影响钾去极化引起的钙摄取。RCM引起的PI的32Pi标记增加与钙摄取没有直接关系，因为变化方向是错误的。RCM对质膜的扰动可能会导致对其他膜成分和系统的抑制。高渗状态也可能导致对膜成分的抑制。尚不清楚这些作用在临床上观察到的RCM毒性中是否重要。
