Histidyl-proline diketopiperazine, an endogenous brain peptide that inhibits (Na + + K +)-ATPase

Abstract

Summary Histidyl-proline diketopiperazine, a metabolite of thyrotropin releasing hormone, has been detected in brain and has a variety of biological activities, both in the pituitary and the central nervous system. An investigation of the biochemical basis for the physiological actions of the peptide has shown that it is an inhibitor of dopamine uptake in nerve endings. The inhibition by the peptide of catecholamine transport, which is sodium-dependent, is due to an inhibition of the brain plasma membrane (Na+ + K+)-ATPase. These findings suggest that histidyl-proline diketopiperazine may be an inhibitor of many membrane transport processes dependent on ion gradients.