Tissue-specific alterations of binding sites for peripheral-type benzodiazepine receptor ligand [3H]PK11195 in rats following portacaval anastomosis.
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 sham-operated 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.
Rao
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Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Quebec, Canada.
Audet
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Therrien
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Butterworth
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RF
D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
D007546:Isoquinolines; D011963:Receptors, GABA-A; C037850:PK 11195