Methylxanthine treatment of rats reduces 2,5-oligoadenylate synthesis in liver nuclei.
The in vivo effects of methylxanthines on 2',5'-oligoadenylate (2,5An) synthetase activity, an interferon-inducible enzyme, were investigated in rat liver nuclei. Caffeine given at 50 mg/kg ip or theobromine given at 80 mg/kg sc twice daily for 5 d resulted in a 60% reduction (p less than 0.01 and p less than 0.05, respectively) of 2,5An synthetase activity in liver nuclei. Theophylline given at 80 mg/kg sc by the same regimen reduced the enzyme activity by 42% (p less than 0.05). Nuclear 2'-phosphodiesterase activity, which catalyzes the degradation of 2,5An, remained low and unchanged following the drug treatments. When animals receiving caffeine were also given the interferon inducer poly(I)poly(C) at 500 micrograms/kg ip once daily for the last 2 d of caffeine treatment, it resulted in the same fourfold increase in 2,5An synthetase activity as shown with poly(I)poly(C) alone. These results suggest that methylxanthines may interact with interferon-mediated actions. The reason for the inhibitory effect of methylxanthines on the basal but not on the induced 2,5An synthetase remains to be investigated.
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D000818:Animals; D002110:Caffeine / Q000633:toxicity*; D002467:Cell Nucleus / Q000201:enzymology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D011070:Poly I-C / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013805:Theobromine / Q000633:toxicity*; D013806:Theophylline / Q000633:toxicity*
D002110:Caffeine; D013806:Theophylline; D015088:2',5'-Oligoadenylate Synthetase; D011070:Poly I-C; D013805:Theobromine