In an attempt to assess the involvement of the 'peripheral-type' benzodiazepine receptors (pBDZR) in hepatic encephalopathy (HE), we examined the binding of the isoquinoline carboxamide derivative 3H-PK 11,195 to lymphocyte membranes from a group of patients with liver cirrhosis with or without clinical signs of HE and normal controls. Lymphocyte 3H-PK 11,195 binding is saturable, with high affinity and presents the pharmacological specificity corresponding to pBDZR. A significant 40% decrease in the number of 3H-PK 11,195 binding sites, without a concomitant change in the apparent affinity, is observed in the group with HE as compared to the controls, but not in that with liver diseases without HE. The decrease in binding capacity correlates significantly with the clinical grading of HE, but not with age, sex, aetiology of cirrhosis or presence of surgical shunt. In contrast to the reduction of pBDZR, 3H-N-methylscopolamine binding to lymphocyte muscarinic receptors is not affected in HE. These findings are consistent with a role for pBDZR in HE and may stimulate studies of endogenous modulators and pharmacological agents for these receptors in the disease.

A study of 3H-PK 11,195 binding to 'peripheral-type' benzodiazepine receptors on human lymphocytes. Evidence of decreased binding in hepatic encephalopathy.

ROCCA, Paola;BENNA, Paolo;OLIVERO, Giorgio;BERGAMASCO, Bruno
1991

Abstract

In an attempt to assess the involvement of the 'peripheral-type' benzodiazepine receptors (pBDZR) in hepatic encephalopathy (HE), we examined the binding of the isoquinoline carboxamide derivative 3H-PK 11,195 to lymphocyte membranes from a group of patients with liver cirrhosis with or without clinical signs of HE and normal controls. Lymphocyte 3H-PK 11,195 binding is saturable, with high affinity and presents the pharmacological specificity corresponding to pBDZR. A significant 40% decrease in the number of 3H-PK 11,195 binding sites, without a concomitant change in the apparent affinity, is observed in the group with HE as compared to the controls, but not in that with liver diseases without HE. The decrease in binding capacity correlates significantly with the clinical grading of HE, but not with age, sex, aetiology of cirrhosis or presence of surgical shunt. In contrast to the reduction of pBDZR, 3H-N-methylscopolamine binding to lymphocyte muscarinic receptors is not affected in HE. These findings are consistent with a role for pBDZR in HE and may stimulate studies of endogenous modulators and pharmacological agents for these receptors in the disease.
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FERRERO P.; P. ROCCA; GUALERZI A.; BENNA P.; ENRICHENS F.; MAO P.; OLIVERO G.; RAVIZZA L.; BERGAMASCO B.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/33899
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