TRYPTAMINE TOXICITY IN ADRENALECTOMIZED RATS; ITS PREVENTION WITH TRYPTAMINE AND HYDROCORTISONE

¹ Department of Biological Chemistry, Harvard Medical School, and the Cancer Research Institute, New England Deaconess Hospital, Boston, Massachusetts

The lethality of tryptamine was compared in intact and adrenalectomized rats. Given as a single dose, tryptamine was about 2 times more toxic for adrenalectomized rats; given in multiple doses over a 3-hr period it was about 6 times more toxic. Intact rats or adrenalectomized rats treated with hydrocortisone acetate appeared to develop tolerance to tryptamine during the course of the multiple doses because of the combined presence of tryptamine and glucocorticoid, endogenous or exogenous. Apparently the lack of a glucocorticoid prevented the untreated adrenalectomized rats from developing such tolerance. Treatment of adrenalectomized rats with desoxycorticosterone acetate was not effective. Indoleacetic acid and tryptamine were measured in plasma after tryptamine injection to determine whether differences in metabolism of tryptamine could account for the difference in toxicity observed. When ultimately lethal doses were injected into adrenalectomized rats, the rats were found to have significantly higher plasma tryptamine levels (5-fold) and lower indoleacetic acid levels than intact rats. Appropriate treatment of the adrenalectomized rats with tryptamine and hydrocortisone acetate reversed the metabolic differences observed and the toxicity.