1193 THE UREASE INFUSED RAT AS A MODEL OF INBORN ERRORS OF UREA SYNTHESIS

Abstract

Rats treated with intravenous urease become acutely hyper-ammonemic (HA) and have increased tryptophan transport into the brain associated with elevated levels of serotonin and 5-hydroxy indoleacetic acid (HIAA) [Life Sciences 33; 2417, 1983]. We have implanted intraperitoneally 7 and 14 day Alzet osmotic pumps delivering 2.5 U urease/100g/24hr. Mean plasma ammonium levels were (X ± SEM) 64 ± 4 uM baseline and 392 ± 30 uM during urease infusion (p <.01) in 23 rats. HA lasted a mean of 8 days. Plasma amino acids showed a specific elevation in glutamiue 698 ± 57 uM versus baseline 412 ± 19 uM (p <.01) with no alterations in branched chain amino acids or tyrosine levels as is seen in models of portal-systemic shunting. Sham operated animals showed no significant biochemical changes. In the cortex of HA animals, levels of serotonin and HIAA were increased but levels of norepinephrine, dopamine and homovanillic acid were not altered. Food intake decreased more in the HA rats than in those receiving sham surgery -6.9 ± 1.4 vs. -4.6 ± 0.9 g/d. Weight loss was also greater in the HA rats 19.8 ± 4.4 vs. 3.0 ± 1.3 g (p< .01). Thus behaviorally, the HA rats were anorectic, similar to children with inborn errors of urea synthesis, which suggests a relationship between altered serotonin metabolism and anorexia. The urease treated rat may prove useful in studying the neurochemical and behavioral abnormalities associated with inborn errors of urea synthesis and may permit the testing of new therapeutic approaches.