Wild K D, Porreca F, Yamamura H I, Raffa R B
R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12018-21. doi: 10.1073/pnas.91.25.12018.
The temperature dependence of the dissociation constant for the interaction of an opioid delta selective ligand and its receptor was evaluated in three tissues. The change in free energy of this interaction was similar in mouse brain, mouse spinal cord, and NG 108-15 mouse neuroblastoma-rat glioma hybrid cells (delta G(o)' = -13.44, -13.34, and -13.66 kcal.mol-1, respectively). However, the reaction was endothermic and occurred with an increase in entropy in mouse brain and NG 108-15 cells, but it was exothermic and occurred with a negligible change in entropy in mouse spinal cord. These data are consistent with the existence of multiple subtypes of opioid delta receptor, and they further suggest that the opioid delta receptor recently cloned from the NG 108-15 cell line is of the brain subtype. Subtypes of opioid delta receptors may mediate analgesia, but not side-effects, of opiates and thus could be targets for future drug design.
在三种组织中评估了阿片δ选择性配体与其受体相互作用的解离常数的温度依赖性。这种相互作用的自由能变化在小鼠脑、小鼠脊髓和NG 108-15小鼠神经母细胞瘤-大鼠胶质瘤杂交细胞中相似（δG(o)'分别为-13.44、-13.34和-13.66 kcal·mol-1）。然而，该反应在小鼠脑和NG 108-15细胞中是吸热的，且伴随着熵的增加，但在小鼠脊髓中是放热的，且熵的变化可忽略不计。这些数据与阿片δ受体存在多种亚型一致，并且进一步表明最近从NG 108-15细胞系克隆的阿片δ受体属于脑亚型。阿片δ受体亚型可能介导阿片类药物的镇痛作用而非副作用，因此可能成为未来药物设计的靶点。
