Evidence for the presence of immunoreactive histidyl-proline diketopiperazine [Cyclo (His-Pro)] in the adult human brain

The current study was undertaken to evaluate the presence of cyclo (His-Pro) in adult human brain tissues obtained at autopsy. We found evidence for immunoreactive cyclo (His-Pro), which diluted in parallel to the radioimmunoassay standard curve and which had mobility on HPLC that was similar to synthetic cyclo (His-Pro), in several regions of the adult human brain. Whereas the levels of cyclo (His-Pro) in the pituitary stalk-median eminence were high (2.2 ng/mg protein), the concentrations in the whole hypothalamus were much lower (0.105 ng/mg protein). Among the extrahypothalamic brain regions examined, the levels of cyclo (His-Pro) were highest in the cerebellar hemisphere (0.168 ng/mg protein) and olfactory bulbs (0.180 ng/mg protein) and were lowest in the hippocampus (0.080 ng/mg protein) and occipital cortex (0.079 ng/mg protein). Thus, immunoreactive cyclo (His-Pro) has widespread distribution in the adult human brain and the potential exists for this cyclic diepeptide to play a role in human brain function.