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Tissue-specific alterations of binding sites for peripheral-type benzodiazepine receptor ligand [3H]PK11195 in rats following portacaval anastomosis

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Abstract

Kinetics of binding of [3H]PK11195, an antagonist ligand with high selectivity for the peripheral-type (mitochondrial) benzodiazepine receptor (PTBR), was studied in homogenates of cerebral cortex, kidney, heart, and testis of portacaval shunted rats and shamoperated controls. Portacaval anastomosis resulted in a significant two- to threefold increase in the number of [3H]PK11195 binding sites in cerebral cortex and kidney. A reduction in the number of [3H]PK11195 binding sites was observed in testis preparations, while the number of binding sites in the heart remained unaltered. These differences in the response of PTBRs to portacaval anastomosis, in different organs suggest that the physiological function of these receptors and the factors regulating them are modulated by distinct mechanisms. The finding of increased densities of [3H]PK11195 binding sites in brain and kidney following portacaval anastomosis parallels the cellular hypertrophy in these tissues and, together with previous observations of similar increases of these binding sites in brain and kidney in congenital hyperammonemia, suggest a pathophysiologic role for ammonia in these changes. In contrast, the significant loss of [3H]PK11195 binding sites in testicular preparations following portacaval anastomosis together with the known effects of steroid hormones on these sites suggests a role for PTBRs in the pathogenesis of testicular atrophy in chronic liver disease.

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Authors and Affiliations

  1. From the Neuroscience Research Unit, Hôpital Saint-Luc, (University of Montreal), H2X 3J4, Montreal, Quebec, Canada

    V. L. Raghavendra Rao, Robert Audet, Guy Therrien &  Roger F. Butterworth

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  1. V. L. Raghavendra Rao
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  2. Robert Audet
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  3. Guy Therrien
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  4. Roger F. Butterworth
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Raghavendra Rao, V.L., Audet, R., Therrien, G. et al. Tissue-specific alterations of binding sites for peripheral-type benzodiazepine receptor ligand [3H]PK11195 in rats following portacaval anastomosis. Digest Dis Sci 39, 1055–1063 (1994). https://doi.org/10.1007/BF02087558

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  • DOI: https://doi.org/10.1007/BF02087558

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