The effect of aminothiadiazole on glycogenesis and glycogenolysis in fetal and neonatal rat liver.

The effect of the teratogen 2-amino-1,3,4-thiadiazole on glycogenesis and glycogenolysis was investigated in the fetal and neonatal rat liver. At day 15, 16, or 17 of gestation (sperm day = day 0) pregnant Sprague-Dawley rats received a single IP injection of an aqueous solution of aminothiadiazole. Dosages used were teratogenic (100 mg/kg maternal body weight) and nonteratogenic (10 mg/kg). At day 16 some rats received nicotinamide (100 mg/rat) in addition to a teratogenic dose of aminothiadiazole. Livers were recovered for assay at fetal day 20 and postnatal day 1. Only at day 16 did a teratogenic dose induce a significant depression in the fetal activity of glycogen synthetase (to 49.6% of control activity) and glucose-6-phosphatase (to 72.2% of control activity), and in glycogen accumulation (to 72.6% of control accumulation). At day 15, a teratogenic dose significantly depressed glucose-6-phosphatase activity but not glycogen synthetase activity or glycogen accumulation. Nicotinamide, given immediately after aminothiadiazole, was effective in blocking the inhibition. Teratogenic treatment had no effect on the postnatal activity of glucose-6-phosphatase. Apparently some event associated with birth releases the enzyme from its prenatal inhibition. These results demonstrate a parallelism between the perturbing effect of aminothiadiazole on biochemical development and morphological development with respect to time of insult, dose response, and protection with its antiteratogen. The mechanism of action whereby aminothiadiazole depresses the activity of glycogen synthetase and glucose-6-phosphatase remains to be determined.