The ontogeny of peptidases involved in the post-transitional processing of cholecystokinin

Abstract

There are three levels at which biologically active peptides may be regulated: transcription, translation, and post-translational processing. The data presented in this study focused on post-translational processing to illustrate the presence and significance of neuropeptide processing and metabolic enzymes in regulating levels and forms of cholecystokinin detected by radioimmunoassay. The activity of the processing enzyme, carboxypeptidase H (EC 3.4.17.10, CPH) and the metabolic enzyme, neutral endopeptidase (EC 3.4.24.11, NEP), were altered by postnatal age 4 days (P4) in central nervous system (CNS) regions. Metallo endopeptidase (EC 3.4.24.15), another metabolic enzyme of cholecystokinin (CCK) has a more constant activity throughout development of the CNS than did CPH or NEP. For enteric nervous system regions, CPH activity showed no change in the more proximal tissues (stomach, duodenum and jejunum) but decreased in distal tissues (midjejunum and ileum) with development. NEP activity decreased with age around P30 in the proximal regions and P4 in more distal regions of the enteric nervous system. Dramatic changes in CCK-like immunoreactivity appear to occur from P4 to P7 in the central nervous system and vary considerably by region. In general, large molecular weight forms of cholecystokinin (L8D-IR) did not change with development in either the central or enteric nervous system regions. Moderate molecular weight forms (I11H-IR) show a regional alteration in the central nervous system whereas these forms decreased in the enteric nervous system. Carboxy-extended (D10Y-IR) forms showed regional alterations in both the central and enteric nervous systems. Bioactive cholecystokinin forms (G17-IR) increased in the enteric nervous system but showed regional alterations in the central nervous system with development. These data suggest that post-translational enzymes aid in regulating the levels and forms of cholecystokinin detected in the central and enteric nervous systems.