Serotonin metabolism in the central nervous system following sepsis or portacaval shunt in the rat.

Similar neurological disturbances and metabolic alterations have been observed in liver insufficiency and in bacterial sepsis. In both liver failure and sepsis an altered neurotransmitter profile in the central nervous system (CNS) has been implicated in the pathogenesis of encephalopathic symptoms. It has been suggested that equivalent disturbances in brain neurotransmitters, especially serotonin, play a role in the encephalopathy accompanying sepsis and liver failure. The objective of this study was to compare the CNS serotonin metabolism in rats with an end-to-side portacaval shunt (PCS) with that found in rats with 12 or 24 hr of intraabdominal sepsis. The metabolism of CNS serotonin was estimated after inhibition of two enzymes acting in the 5-hydroxyindole synthetic pathway (decarboxylase and monoamine oxidase). The 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined in different regions of the CNS, thereby permitting evaluation of the synthetic activity of the serotonin neurotransmitter system. As previously reported, a marked increase in CNS serotonin synthetic rate was noted following PCS. In contrast, and in contradistinction to several recent reports, no major changes in the CNS serotonin synthesis rate were present following 12 or 24 hr of sepsis. CNS levels of the serotonin metabolite 5-HIAA were elevated in both sepsis and PCS rats. These data indicate that sepsis and liver failure have different effects upon serotonin metabolism in the CNS and suggest that differing pathogenetic mechanisms may underlie the encephalopathy clinically associated with these conditions.

Excretion of 5-S-cysteinyldopa in the urine of healthy subjects.

Seventy-six Caucasians, 30 men and 46 women, were investigated for the 24-hour excretion of 5-S-cysteinyl dopa in the urine during the months of September to November, 1973. No subject had had strong sun exposure for at least 4 weeks prior. A preliminary finding of a variation of 5-S-cysteinyldopa with season necessitated this precaution. The excretion varied between 9.0 and 242 mug/24 hours. The mean value in men was 100 mug/24 hours and in women 77.8 mug/24 hours. Subjects with white hair had lower values than those with pigmented hair, but there was no other difference between the excreted amounts in subjects with differing hair colour. There was no variation with age when the subjects with white hair were excluded. No variation with weight or body surface was found. Excretion of dopa and dopamine determined together did not correlate with the excretion of 5-S-cysteinyldopa.