DEGRADATION OF ACTH MSH(4-10) AND ITS SYNTHETIC ANALOG SEMAX BY RAT SERUM ENZYMES - AN INHIBITOR STUDY/

Degradation of the behaviorally active peptide ACTH/MSH(4-10) and its synthetic analog semax was studied in serum in the presence of several specific peptidase inhibitors. Bestatin and puromycin were used to in hibit aminopeptidase activity, lisinopril for angiotensin-converting e nzyme, phosphoramidon for neutral endopeptidase 24.11, and Z-Pro-proli nal for prolyl endopeptidase. Bestatin inhibited up to 66%, puromycin about 33%, and lisinopril about 15% of total degrading activity agains t both ACTH/MSH(4-10) and semax. Involvement of neutral endopeptidase and prolyl endopeptidase in hydrolysis of the two peptides was less de finitive. These studies showed that aminopeptidases and angiotensin-co nverting enzyme are responsible for the major part of the hydrolysis o f ACTH/MSH(4-10) and semax in rat serum.