Low doses of L-tryptophan are lethal in rats with adrenal insufficiency.
Adrenalectomy decreased the LD50 value for L-tryptophan from greater than 1000 mg/kg in normal rats to 11.6 mg/kg. The LD50 in adrenalectomized rats was restored to normal by corticosterone replacement therapy. Administration of metyrapone, which blocks the synthesis of adrenal steroids, to normal rats decreased plasma corticosterone levels by approximately 50% and decreased the LD50 from greater than 1000 mg/kg to 24.9 mg/kg. Neurochemical analysis revealed a large increase in tissue tryptamine levels following administration of L-tryptophan in rats with adrenal insufficiency. Therefore, it appears that death due to L-tryptophan in animals with adrenal insufficiency is due to formation of excess tryptamine and, consequently, an elevation in blood pressure and other cardiovascular dysfunctions.
Trulson
M E
ME
Ulissey
M J
MJ
D000309:Adrenal Insufficiency / Q000503:physiopathology; D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D007928:Lethal Dose 50; D008099:Liver / Q000378:metabolism; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000378:metabolism / Q000633:toxicity*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D014364:Tryptophan; D014366:Tryptophan Oxygenase; D003345:Corticosterone; D008797:Metyrapone