Borowitz J L, Gunasekar P G, Isom G E
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Brain Res. 1997 Sep 12;768(1-2):294-300. doi: 10.1016/s0006-8993(97)00659-8.
Hydrogen cyanide, a gaseous molecule, is produced by white blood cells during phagocytosis. The present study examined the possibility that neuronal-like cells may also produce cyanide following activation. Rat pheochromocytoma (PC12) cells exhibited a low level of cyanide generation that was significantly increased by mu-opiate agonists (hydromorphone, morphine) and blocked by naloxone. A variety of other agonists including bradykinin, nicotine and glutamate did not generate cyanide in PC12 cells. Systemic administration of hydromorphone to rats increased brain cyanide levels by 61% after 15 min. Using microdialysis probes implanted in the cortical-hippocampal areas of the anesthetized rat or in the hypothalamus of the conscious hamster, a 2- to 5-fold increase in cyanide generation was seen after hydromorphone administration and this increase was blocked by naloxone. To determine whether cyanide release by hydromorphone has functional significance in a neuronal system, cyanide enhancement of N-methyl-D-aspartate (NMDA)-induced increased [Ca2+]i was measured in rat cerebellar granule cells. Hydromorphone enhanced the response to NMDA similar to cyanide and the hydromorphone effect was blocked by cyanide scavengers. These data show that cyanide generation is increased in neuronal tissue by a mu-opiate receptor agonist and it is proposed that endogenous cyanide may modulate the NMDA receptor response.
氰化氢是一种气态分子，由白细胞在吞噬作用过程中产生。本研究探讨了神经元样细胞在激活后也可能产生氰化物的可能性。大鼠嗜铬细胞瘤（PC12）细胞产生氰化物的水平较低，μ-阿片受体激动剂（氢吗啡酮、吗啡）可使其显著增加，而纳洛酮可阻断这一增加。包括缓激肽、尼古丁和谷氨酸在内的多种其他激动剂在PC12细胞中不会产生氰化物。给大鼠全身注射氢吗啡酮15分钟后，脑内氰化物水平增加了61%。使用植入麻醉大鼠皮质-海马区或清醒仓鼠下丘脑的微透析探针，注射氢吗啡酮后可见氰化物生成增加2至5倍，且这种增加被纳洛酮阻断。为了确定氢吗啡酮释放氰化物在神经元系统中是否具有功能意义，在大鼠小脑颗粒细胞中测量了氰化物增强N-甲基-D-天冬氨酸（NMDA）诱导的细胞内钙离子浓度（[Ca2+]i）升高的情况。氢吗啡酮增强了对NMDA的反应，类似于氰化物，且氢吗啡酮的作用被氰化物清除剂阻断。这些数据表明，μ-阿片受体激动剂可使神经元组织中的氰化物生成增加，并且有人提出内源性氰化物可能调节NMDA受体反应。
