Morphine enhances purine nucleotide catabolism in vivo and in vitro

摘要

＜正＞ Aim:To investigate the effect and mechanism of morphine on purine nucleotidecatabolism.Methods:The rat model of morphine dependence and withdrawal andrat C6 glioma cells in culture were used.Concentrations of uric acid in the plasmawere measured by the uricase-rap method,adenosine deaminase（ADA）and xan-thine oxidase（XO）in the plasma and tissues were measured by the ADA and XOtest kit.RT-PCR and RT-PCR-Southern blotting were used to examine the relativeamount of ADA and XO gene transcripts in tissues and C6 cells.Results:（i）theconcentration of plasma uric acid in the morphine-administered group was signifi-cantly higher（P＜0.05）than the control group;（ii）during morphine administrationand withdrawal periods,the ADA and XO concentrations in the plasma increasedsignificantly（P＜0.05）;（iii）the amount of ADA and XO in the parietal lobe,liver,small intestine,and skeletal muscles of the morphine-administered groupsincreased,while the level of ADA and XO in those tissues of the withdrawalgroups decreased;（iv）the transcripts of the ADA and XO genes in the parietallobe,liver,small intestine,and skeletal muscles were higher in the morphine-administered group.The expression of the ADA and XO genes in those tissuesreturned to the control level during morphine withdrawal,with the exception of theskeletal muscles;and（v）the upregulation of the expression of the ADA and XOgenes induced by morphine treatment could be reversed by naloxone.Conclusion:The effects of morphine on purine nucleotide metabolism might be an important,new biochemical pharmacological mechanism of morphine action.