Increased Densities of Binding Sites for the Peripheral-Type Benzodiazepine Receptor Ligand [3H]PK 11195 in Congenital Ornithine Transcarbamylase-Deficient Sparse Fur Mouse

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Abstract

ABSTRACT

Peripheral-type (mitochondrial) benzodiazepine receptors (PTBR) were studied in the brain and peripheral organs (kidney, liver, and testis) of normal male mice (CD-1/Y) and the congenially hyperammonemic sparse fur (spf/Y) mouse. Radioligand binding assays were performed with [3H]PK 11195, a ligand with high selectivity and affinity for PTBR. Densities (maximal number of binding sites) of [3H]PK 11195 binding sites were greatest in kidney, followed by liver, testis, and brain. Densities of [3H]PK 11195 binding sites were significantly increased in all tissues of spf mice compared with control animals. In view of the localization of PTBR on the outer mitochondrial membrane, changes in PTBR in spf mouse tissues may modulate the altered mitochondrial function and oxidative metabolism, in brain and peripheral tissues, in congenital OTC deficiency. The positron emission tomography ligand 11C-PK 11195 could find an application in the assessment of end organ dysfunction in this disorder.

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