Neurotransmitter receptor imbalances in motor cortex and basal ganglia in hepatic encephalopathy.
Hepatic encephalopathy (HE) in chronic liver disease is characterized by neuropsychiatric and motor disturbances and associated with a net increase of inhibitory neurotransmission. Though many studies, mostly carried out in animal models, have linked dysfunctions of single neurotransmitter systems with the pathogenesis of HE, reports concerning neurotransmitter receptor alterations are controversial. Little is known about the situation in humans. We carried out a multireceptor assessment of HE-associated changes in neurotransmitter receptor densities and affinities in human post-mortem brain samples. Dissociation constants and densities of different binding sites for glutamate, GABA, acetylcholine, norepinephrine, serotonin, dopamine and adenosine were determined by in vitro binding assays and quantitative receptor autoradiography in the motor cortex and putamen of HE and control brains. HE cases do not build a homogeneous group, but differ concerning direction and intensity of binding site density divergences from control values. The acetylcholine M2 binding site dissociation constant was significantly higher in HE brains. Nicotinic acetylcholine and adenosine type 1 and 2A densities were significantly down-regulated in the putamen of HE brains. Our data suggest that neurotransmitter alterations are probably not the primary key factor responsible for the neuropsychiatric and motor disturbances associated with HE.
Palomero-Gallagher
Nicola
N
Institute of Neurosciences and Medicine (INM-2), Research Center Jülich, Jülich, Germany. n.palomero-gallagher@fz-juelich.de
Bidmon
Hans-Jürgen
HJ
Cremer
Markus
M
Schleicher
Axel
A
Kircheis
Gerald
G
Reifenberger
Guido
G
Kostopoulos
George
G
Häussinger
Dieter
D
Zilles
Karl
K
D000109:Acetylcholine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000328:Adult; D000368:Aged; D001345:Autoradiography; D001479:Basal Ganglia / Q000503:physiopathology*; D001665:Binding Sites; D016022:Case-Control Studies; D004298:Dopamine / Q000378:metabolism; D017809:Fatal Outcome; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000503:physiopathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism* / Q000503:physiopathology*; D009638:Norepinephrine / Q000378:metabolism; D011485:Protein Binding; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D017981:Receptors, Neurotransmitter; D012701:Serotonin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D000109:Acetylcholine; D004298:Dopamine; D009638:Norepinephrine