Action of Actinomycin D on Tryptophan Uptake in the Adrenalectomized Rat and Its Effect on Induction of Tryptophan Pyrrolase and Tyrosine Transaminase in Liver

Abstract

Abstract Orally intubated 3H-labeled tryptophan was retained significantly in the stomach and intestine of rats treated with actinomycin D (43%) as compared to controls (13%) 4 hours after intubation. Likewise, smaller amounts of the isotope subsequently appeared in the liver and serum of the drug-treated animals. In contrast, actinomycin had no effect on movement of intraperitoneally injected 3H-tryptophan out of the peritoneal cavity or its subsequent accumulation in the liver. Induction of tryptophan pyrrolase by intraperitoneally or intravenously administered tryptophan was unaffected by concomitant actinomycin D treatment. On the other hand, similar induction of tyrosine transaminase was completely blocked by the drug. When l-tryptophan was administered orally over a range of 5 to 20 mg/100 g, the maximum induction of tyrosine transaminase was obtained at the 5-mg dose with no further enhancement at higher levels. However, with tryptophan pyrrolase, there was a gradual response: no induction after 5 mg, a 3-fold increase at 10 mg, and a 6-fold enhancement at 20 mg. These experiments show that in the rat actinomycin D affects the transport and absorption of dietary metabolites from the gastrointestinal tract. Therefore it is important to consider any conclusion drawn from orally administered substrate induction experiments in the light of this action of actinomycin D.