CNS tryptamine metabolism in hepatic coma

Abstract

Lumbar CSF indoleacetic acid (IAA) was higher in patients with cirrhosis of the liver than in controls. It was also higher in CSF of patients in coma than in those with hepatic cirrhosis but not in coma. There was a strong correlation (r = 0.89, p less than 0.01) between the grade of hepatic coma and CSF IAA. These data indicate that there is an association between elevated CNS tryptamine metabolism and hepatic coma. How far changes in the metabolism of tryptamine and other trace amines are relevant to the induction of hepatic coma or are simply a reflection of advanced liver dysfunction is unclear.

Increased brain serotonin turnover correlates with the degree of shunting and hyperammonemia in rats following variable portal vein stenosis

“…These results confirm and extend earlier observations of significant increases in the concentrations of these amino acids in the brains of rats following complete PCA [8,30,31] and in autopsied brain tissue [27,32] and CSF [15,16] of cirrhotic patients with HE. It is well established that, as a result of PSS, large amounts of ammonia bypass the liver and accumulate in the brain, where ammonia is detoxified by amidation to glutamine.…”

“…Studies in experimental animals reveal significant alterations in the dopaminergic [2], serotoninergic [1,3 -7], and histaminergic [7,8 -11] systems following complete end-to-side portacaval anastomosis (PCA) in the rat. In addition, changes in the concentrations of monoamines and metabolites, as well as altered monoamine receptor densities have been reported in autopsied brain tissue [12 -14] and CSF [15,16] of cirrhotic patients with HE. Relating these findings to the clinical presentation of HE it has been suggested that some of the early neuropsychiatric symptoms, such as inverted sleep patterns and altered circadian rhythms may result from changes in serotoninergic and histaminergic neurotransmission, whereas motor dysfunction has been attributed to a dopaminergic deficit in brain.…”

Current Theories on the Pathogenesis of Hepatic Encephalopathy

“…Increased availability of the amino acid precursor during chronic liver failure may promote the synthesis of alternate neuroactive tryptophan metabolites, in addition to the biogenic amine serotonin, including neuroactive intermediates in the kynurenine pathway and tryptamine (see below). It was demonstrated, for example, that hepatic dysfunction altered CNS concentrations of both tryptamine in humans (57,65,66) and quinolinic acid in both human and experimental animals (41,42). Although much of the focus in the study of HE shifted in the early 1980s to the GABA system and its potential as a causative agent in HE (discussed below), there is recent data which suggest that the amine systems, and in particular the metabolites of tryptophan, may play specific and important roles in the pathogenesis of the neuropsychiatric symptoms of HE.…”

Increase in the Content of Quinolinic Acid in Cerebrospinal Fluid and Frontal Cortex of Patients with Hepatic Failure

“…An increased availability oftryptophan to the brain seems to contribute to the pathophysiology and s y m p tomatology of hepatic encephalopathy (On0 et al, 1978;Jellinger et al, 1978). Postulated mechanisms include an increased synthesis and utilization of Shydroxytryptamine (5-HT) (On0 et al, 1978;Jellinger et al, 1978) and/or of tryptamine (Young and Lal, 1980). It has been recently shown that quinolinic acid (QUIN), another tryptophan metabolite (Gholson et al, 1964), is an agonist of the receptors for excitatory amino acids (Stone and Perkins, 1981;Perkins and Stone, 1982).…”