Increased density of brain histamine H(1) receptors in rats with portacaval anastomosis and in cirrhotic patients with chronic hepatic encephalopathy.
The binding properties and the regional densities of histamine H(1) receptors were studied in brain of rats with portacaval anastomosis (PCA) and in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy (HE). Receptor binding studies and quantitative receptor autoradiography were performed, employing [(3)H]mepyramine. Histamine H(1) receptors in rat brain displayed a higher density and a lower affinity compared with control human frontal cortex. Specific [(3)H]mepyramine binding was heterogeneously distributed throughout the brain in both species. In human brain, binding was highest in the parietal and temporal cortices and lowest in caudate-putamen. In rat brain, binding was highest in the suprachiasmatic nucleus, dentate gyrus of the hippocampus, ventromedial hypothalamus, and nucleus accumbens. Cortical tissue from PCA rats and frontal cortical tissue from HE patients contained significantly increased densities (B(max)) of H(1) receptors. A selective increase in H(1) receptor density was also observed in parietal and insular cortices of HE patients. Results of the present study suggest a selective up-regulation of brain H(1) receptors in PCA rats and in patients with HE. The central histaminergic system is implicated in the control of arousal and circadian rhythmicity. Previous studies have shown that blockade of H(1) receptors in PCA rats results in improved locomotor activity and circadian rhythmicity scores. The present findings suggest that cortical histaminergic hyperactivity could contribute to the neuropsychiatric symptoms characteristic of human HE, and that selective histamine H(1) receptor antagonists could be beneficial in the prevention and treatment of some of the symptoms of HE in cirrhotic patients.
Lozeva
V
V
Neuroscience Research Unit, Centre Hospitalier de l'Université de Montréal, Campus St-Luc, Montreal, Quebec, Canada.
Tuomisto
L
L
Sola
D
D
Plumed
C
C
Hippeläinen
M
M
Butterworth
R
R
D000368:Aged; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D006501:Hepatic Encephalopathy / Q000150:complications*; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000378:metabolism*
D011969:Receptors, Histamine H1