Morphine enhances purine nucleotide catabolism in vivo and in vitro.
OBJECTIVE
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.


CONCLUSIONS
The effects of morphine on purine nucleotide metabolism might be an important, new biochemical pharmacological mechanism of morphine action.
Liu
Chang
C
Department of Biochemistry and Molecular Biology, Basic Medical School, Jilin University, Jilin, China.
Liu
Jian-kai
JK
Kan
Mu-jie
MJ
Gao
Lin
L
Fu
Hai-ying
HY
Zhou
Hang
H
Hong
Min
M
D000243:Adenosine Deaminase / Q000032:analysis / Q000235:genetics; D000818:Animals; D001806:Blood Urea Nitrogen; D045744:Cell Line, Tumor; D005260:Female; D009020:Morphine / Q000494:pharmacology*; D011685:Purine Nucleotides / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000032:analysis / Q000235:genetics
D011685:Purine Nucleotides; D012333:RNA, Messenger; D014527:Uric Acid; D009020:Morphine; D014969:Xanthine Oxidase; D000243:Adenosine Deaminase