Abstract
Aim:
To investigate the effect and mechanism of morphine on purine nucleotide catabolism.
Methods:
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.
Results:
(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.
Conclusion:
The effects of morphine on purine nucleotide metabolism might be an important, new biochemical pharmacological mechanism of morphine action.
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Liu, C., Liu, Jk., Kan, Mj. et al. Morphine enhances purine nucleotide catabolism in vivo and in vitro. Acta Pharmacol Sin 28, 1105–1115 (2007). https://doi.org/10.1111/j.1745-7254.2007.00592.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00592.x