M. Atmaca et Jr. Fry, ADENOSINE-MEDIATED INHIBITION OF GLUTATHIONE SYNTHESIS IN RAT ISOLATED HEPATOCYTES, Biochemical pharmacology, 52(9), 1996, pp. 1423-1428
The modulatory effect of adenosine on hepatic glutathione (GSH) synthe
sis has been investigated in an experimental model in which GSH synthe
sis from methionine was monitored in rat isolated hepatocytes previous
ly depleted of GSH. Adenosine inhibited GSI-I synthesis in this system
, with complete inhibition occurring at 1 mM. Studies with adenosine r
eceptor agonists and antagonists and adenosine analogues devoid of ago
nist activity have indicated that this effect of adenosine is not rece
ptor-mediated nor is it mediated through changes in ATP level or redox
balance. Rather, the data are consistent with an inhibitory effect of
adenosine on the methionine-->cysteine transsulphuration pathway, pro
bably at the level of the enzyme S-adenosylhomocysteine hydrolase. Sub
maximal inhibitory concentrations of adenosine produced an effect on G
SH synthesis additive to that obtained with a maximal inhibitory conce
ntration oi adrenaline, which inhibits GSH synthesis at the level of g
amma-glutamylcysteinyl synthetase. Furthermore, exposure of hepatocyte
s to adenosine subsequent to brief treatment with the toxicant menadio
ne precipitated cytotoxicity. These results suggest that adenosine-med
iated inhibition of hepatic GSH synthesis may have a role in various p
athological or toxicological states. Copyright (C) 1996 Elsevier Scien
ce Inc.