Increased concentrations of histamine and its metabolite, tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma.
OBJECTIVE
Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of chronic liver disease. To determine whether changes in the central histaminergic system are a feature of human HE, we studied histamine, tele-methylhistamine, and presynaptic autoregulatory H(3) receptors in cerebral cortex and caudate-putamen obtained at autopsy from six cirrhotic patients and six appropriately matched controls.


METHODS
Histamine was assayed by HPLC; tele-methylhistamine by GC-MS. H(3) receptors were studied by in vitro receptor binding using [3H]R-alpha-methylhistamine as ligand.


RESULTS
In HE patients, there was a significant fourfold increase of histamine in caudate-putamen and a significant increase in all cortical regions studied. tele-Methyhistamine was also increased and the densities of histamine H(3) receptor sites were significantly decreased in patient material.


CONCLUSIONS
These findings are consistent with activation of the histaminergic system in HE. Given that histamine participates in the regulation of arousal and circadian rhythmicity, they indicate that induction of central histamine mechanisms may contribute to the development of neuropsychiatric symptoms, such as sleep disturbances and altered circadian rhythms in chronic HE and suggest that pharmacological manipulation of the histaminergic system could be beneficial in the treatment of HE in chronic liver failure.
Lozeva
Violina
V
Neuroscience Research Unit, Centre Hospitalier de l'Université de Montréal, Hôpital Saint-Luc, 1058 St.-Denis St., Montreal, Quebec, Canada H2X 3J4.
Tuomisto
Leena
L
Tarhanen
Juhani
J
Butterworth
Roger F
RF
D000328:Adult; D000368:Aged; D001923:Brain Chemistry; D016022:Case-Control Studies; D015536:Down-Regulation; D006501:Hepatic Encephalopathy / Q000401:mortality*; D006632:Histamine / Q000032:analysis*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008761:Methylhistamines / Q000032:analysis*; D008875:Middle Aged; D009994:Osmolar Concentration; D018100:Receptors, Histamine H3 / Q000032:analysis*
D008761:Methylhistamines; D018100:Receptors, Histamine H3; D006632:Histamine; C020404:tele-methylhistamine