TY  - JOUR
AU  - Palomero-Gallagher, N.
AU  - Bidmon, H.-J.
AU  - Cremer, M.
AU  - Schleicher, A.
AU  - Kircheis, G.
AU  - Reifenberger, G.
AU  - Kostopoulos, G.
AU  - Häussinger, D.
AU  - Zilles, K.
TI  - Neurotransmitter Receptor Imbalances in Motor Cortex and Basal Ganglia in Hepatic Encephalopathy
JO  - Cellular physiology and biochemistry
VL  - 24
SN  - 1015-8987
CY  - Basel
PB  - Karger
M1  - PreJuSER-5301
PY  - 2009
N1  - The authors thank S. Wilms, S. Krause and A. Borner for excellent technical assistance. This project was supported by the Deutsche Forschungsgemeinschaft through the Sonderforschungsbereich 575 "Experimental Hepatology" (project C5).
AB  - 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.
KW  - Acetylcholine: metabolism
KW  - Adenosine: metabolism
KW  - Adult
KW  - Aged
KW  - Autoradiography
KW  - Basal Ganglia: physiopathology
KW  - Binding Sites
KW  - Case-Control Studies
KW  - Dopamine: metabolism
KW  - Fatal Outcome
KW  - Female
KW  - Glutamic Acid: metabolism
KW  - Hepatic Encephalopathy: physiopathology
KW  - Humans
KW  - Liver Cirrhosis: metabolism
KW  - Liver Cirrhosis, Alcoholic: metabolism
KW  - Male
KW  - Middle Aged
KW  - Motor Cortex: metabolism
KW  - Motor Cortex: physiopathology
KW  - Norepinephrine: metabolism
KW  - Protein Binding
KW  - Receptors, Neurotransmitter: metabolism
KW  - Serotonin: metabolism
KW  - gamma-Aminobutyric Acid: metabolism
KW  - Receptors, Neurotransmitter (NLM Chemicals)
KW  - Serotonin (NLM Chemicals)
KW  - Norepinephrine (NLM Chemicals)
KW  - Acetylcholine (NLM Chemicals)
KW  - gamma-Aminobutyric Acid (NLM Chemicals)
KW  - Glutamic Acid (NLM Chemicals)
KW  - Adenosine (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:19710544
UR  - <Go to ISI:>//WOS:000268679900018
DO  - DOI:10.1159/000233254
UR  - https://juser.fz-juelich.de/record/5301
ER  -