ENDOGENOUS BENZODIAZEPINE RECEPTOR LIGANDS IN HUMAN AND ANIMAL HEPATIC-ENCEPHALOPATHY

被引：110

作者：

OLASMAA, M

ROTHSTEIN, JD

GUIDOTTI, A

WEBER, RJ

PAUL, SM

SPECTOR, S

ZENEROLI, ML

BARALDI, M

COSTA, E

机构：

[1] GEORGETOWN UNIV,SCH MED,FIDIA GEORGETOWN INST NEUROSCI,3900 RESERVOIR RD NW,WASHINGTON,DC 20007

[2] JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205

[3] NIDDK,NEUROIMMUNOL UNIT,MED CHEM LAB,BETHESDA,MD

[4] NIMH,BETHESDA,MD 20892

[5] VANDERBILT UNIV,DEPT PHARMACOL & PSYCHIAT,NASHVILLE,TN 37240

[6] UNIV MODENA,DEPT PHARMACOL & PHARMACOGNOSY,I-41100 MODENA,ITALY

来源：

JOURNAL OF NEUROCHEMISTRY | 1990年 / 55卷 / 06期

关键词：

Benzodiazepine; Cerebrospinal fluid; Diazepam binding inhibitor; Hepatic encephalopathy; Liver; γ‐Aminobutyric acid;

D O I：

10.1111/j.1471-4159.1990.tb05790.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Abstract: The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in humans and in rat models of hepatic encephalopathy. Endogenous benzodiazepine ligands were extracted from rat brain and human CSF by acid treatment and purification by HPLC. Detection and partial characterization of these endogenous benzodiazepine ligands were carried out using both radioreceptor binding assays and radioimmunoassays with anti‐benzodiazepine antibodies. Four different benzodiazepine receptor ligands were identified in human and rat tissue, two of which may be diazepam and desmethyldiazepam, based on elution profiles and anti‐benzodiazepine antibody reactivity. Human CSF and serum from patients with hepatic encephalopathy contained ∼ 10 times more endogenous benzodiazepine receptor ligand than CSF from controls or nonencephalopathic patients with liver disease. The levels of brain benzodiazepine receptor ligand compounds were also increased ∼ 10‐fold in rats suffering from fulminant hepatic failure, but not in rats with portacaval shunts, a model of chronic hepatic disease. The increased concentrations of these substances could be behaviorally significant and may contribute to the pathogenesis of hepatic encephalopathy. Copyright © 1990, Wiley Blackwell. All rights reserved

引用

页码：2015 / 2023

页数：9

共 44 条

[1] Bansky G., Meier P.J., Riederer E., Walser H., Ziegler W.H., Schmid M., Effects of the benzodiazepine antagonist flumazenil in hepatic encephalopathy in humans, Gastroemerology, 97, pp. 744-750, (1989)
[2] Baraldi M., Zeneroli M., Experimental hepatic encephalopathy: changes in the binding of γ‐aminobutyric acid, Science, 216, pp. 427-428, (1982)
[3] Baraldi M., Zeneroli M.L., Ventura E., Penne A., Pinelli C., Ricci P., Santi M., Supersensitivity of benzodiazepine receptors in hepatic encephalopathy due to fulminant hepatic failure in the rat: reversal by a benzodiazepine antagonist, Clin. Sci., 67, pp. 167-175, (1984)
[4] Barbaccia M.L., Guarneri P., Berkovich A., Wambebe C., Guidotti A., Costa E., The endogenous modulator of GABAA receptors in affective disorders, The Allosteric Modulation of Amino Acid Receptors and Its Therapeutic Implications, pp. 125-130, (1989)
[5] Basile A.S., Gammal S.H., Mullen K.D., Jones E.A., Skolnick P., Differential responsiveness of cerebellar Purkinje neurons to GABA and benzodiazepine receptor ligands in an animal model of hepatic encephalopathy, J. Neurosci., 8, pp. 2414-2421, (1988)
[6] Basile A.S., Gammal S.H., Jones E.A., Skolnick P., GABAA receptor complex in an experimental model of hepatic encephalopathy: evidence for elevated levels of an endogenous benzodiazepine receptor ligand, J. Neurochem, 53, pp. 1057-1063, (1989)
[7] Bassett M.L., Mullen K.D., Skolnick P., Jones E.A., Amelioration of hepatic encephalopathy by pharmacologic antagonism of the GABAA‐benzodiazepine receptor complex in a rabbit model of fulminant hepatic failure, Gastroenterology, 93, pp. 1069-1077, (1987)
[8] Bradford M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein‐dye binding, Anal. Biochem., 72, pp. 248-254, (1976)
[9] Costa E., Guidotti A., Neuropeptides as cotransmitters: modulatory effects at GABAergic synapses, Psychopharmacology: The Third Generation of Progress, pp. 425-435, (1987)
[10] DeBlas A.L., Sotelo C., Localization of benzodiazepine‐like molecules in the rat brain, A light and electron microscopy immunocytochemistry study with an anti-benzodiazepine monoclonal antibody. Brain Res., 413, pp. 285-296, (1987)

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