Induction of alkaline phosphatase activity in Hela cells. Inhibition by xanthine derivatives and thermostability studies
Wharton, W.; Goz, B.
Biochemical Pharmacology 28(6): 763-768
ISSN/ISBN: 0006-2952 PMID: 88228 DOI: 10.1016/0006-2952(79)90356-3
The induction of alkaline phosphate activity in He La cells by 5-iodo-2′-deoxyuridine (IUd R) or hydrocortisone was inhibited in a dose-dependent manner by the addition of the xanthine derivatives caffeine, theophylline or 3-isobutyl-1-methylxanthine to the culture medium during the 72 hr of the induction. Pretreatment with theophylline from −24 to 0 hr or treatment from 0 to 24 hr with any of the xanthine derivatives was ineffective in inhibiting alkaline phosphatase induction produced by treatment with IUd R from 0 to 72 hr. The induction of alkaline phosphatase activity produced by treatment with hydrocortisone from 0 to 72 hr was inhibited by pretreatment with theophylline from −24 to 0 hr, although this inhibition was only about 60 per cent as great as that seen with treatment from 0 to 72 hr. As judged by heat inactivation studies, IUd R predominantly increased the heat-labile form of alkaline phosphatase activity, while hydrocortisone predominantly increased the heat-stable form. Regardless of the inducer used, the xanthine derivatives mainly decreased the heat-stable form of alkaline phosphatase activity. Treatment with imidazole over a 72-hr period produced over a 2-fold induction of alkaline phosphatase activity, which could be inhibited completely by concurrent treatment with theophylline.