Liu Chang, Liu Jian-kai, Kan Mu-jie, Gao Lin, Fu Hai-ying, Zhou Hang, Hong Min
Department of Biochemistry and Molecular Biology, Basic Medical School, Jilin University, Jilin, China.
Acta Pharmacol Sin. 2007 Aug;28(8):1105-15. doi: 10.1111/j.1745-7254.2007.00592.x.
To investigate the effect and mechanism of morphine on purine nucleotide catabolism.
The rat model of morphine dependence and withdrawal and rat C6 glioma cells in culture were used. Concentrations of uric acid in the plasma were measured by the uricase-rap method, adenosine deaminase (ADA) and xanthine oxidase (XO) in the plasma and tissues were measured by the ADA and XO test kit. RT-PCR and RT-PCR-Southern blotting were used to examine the relative amount of ADA and XO gene transcripts in tissues and C6 cells.
(i) the concentration of plasma uric acid in the morphine-administered group was significantly higher (P<0.05) than the control group; (ii) during morphine administration and withdrawal periods, the ADA and XO concentrations in the plasma increased significantly (P<0.05); (iii) the amount of ADA and XO in the parietal lobe, liver, small intestine, and skeletal muscles of the morphine-administered groups increased, while the level of ADA and XO in those tissues of the withdrawal groups decreased; (iv) the transcripts of the ADA and XO genes in the parietal lobe, liver, small intestine, and skeletal muscles were higher in the morphine-administered group. The expression of the ADA and XO genes in those tissues returned to the control level during morphine withdrawal, with the exception of the skeletal muscles; and (v) the upregulation of the expression of the ADA and XO genes induced by morphine treatment could be reversed by naloxone.
The effects of morphine on purine nucleotide metabolism might be an important, new biochemical pharmacological mechanism of morphine action.
研究吗啡对嘌呤核苷酸分解代谢的作用及机制。
采用吗啡依赖和戒断大鼠模型以及培养的大鼠C6胶质瘤细胞。用尿酸酶-速率法测定血浆中尿酸浓度，用腺苷脱氨酶（ADA）和黄嘌呤氧化酶（XO）检测试剂盒测定血浆和组织中的ADA及XO。采用逆转录-聚合酶链反应（RT-PCR）和RT-PCR- Southern印迹法检测组织和C6细胞中ADA和XO基因转录本的相对量。
（i）吗啡给药组血浆尿酸浓度显著高于对照组（P<0.05）；（ii）在吗啡给药及戒断期间，血浆中ADA和XO浓度显著升高（P<0.05）；（iii）吗啡给药组顶叶、肝脏、小肠和骨骼肌中ADA和XO含量增加，而戒断组这些组织中ADA和XO水平降低；（iv）吗啡给药组顶叶、肝脏、小肠和骨骼肌中ADA和XO基因转录本较高。除骨骼肌外，这些组织中ADA和XO基因的表达在吗啡戒断期间恢复到对照水平；（v）吗啡处理诱导的ADA和XO基因表达上调可被纳洛酮逆转。
吗啡对嘌呤核苷酸代谢的影响可能是吗啡作用的一种重要的新的生化药理学机制。
