The apparent positive cooperativity of in vivo [3H]PK-11195 binding in mouse fibrosarcoma

To evaluate the binding properties of peripheral benzodiazepine receptor (PBR) in mouse fibrosarcoma, [3H]PK-11195 binding, in vitro and in vivo, was investigated using either tissue dissection or autoradiographic method. The binding characteristics in fibrosarcoma were compared with those in the kidney. The results of an in vitro saturation study revealed that the maximal numbers of PBR binding sites (Bmax) in fibrosarcoma and in the kidney were almost the same (kidney: 5.2 pmol/mg protein; fibrosarcoma: 5.0 pmol/mg protein). On the other hand, the binding affinity (Kd) in fibrosarcoma was lower than that in the kidney (kidney: 0.45 nM; fibrosarcoma: 1.34 nM). It is noteworthy that the in vivo binding of [3H]PK-11195 in fibrosarcoma increased with increasing doses of [3H]PK-11195 (in the dose range of 0.03–1 mg/kg), whereas that in the kidney decreased with competitive inhibition. The apparent positive cooperativity of [3H]PK-11195 binding in fibrosarcoma was only observed under in vivo conditions and might be possibly related to the incoordination of PBR subunits.