Reversible down-regulation of liver cyclo(His-Pro) binding sites by cyclo(His-Pro) administration to mice

Intraperitoneal injections of histidyl-proline diketopiperazine [cyclo(His-Pro), 15 mg/kg/day] to mice for 3 days caused a significant loss of cyclo(His-Pro) binding sites in the liver. This loss depended on the decrease in the number of binding sites and not on the change in affinity. The cyclo(His-Pro)-mediated loss was reversible, and the specific binding returned to the original level within 3 days of the cessation of cyclo(His-Pro). These results suggest that cyclo(His-Pro) participates in regulating its own binding sites in the liver.