The biosynthesis of regulatory peptides.

Regulatory peptides are synthesized in their cells of origin as large, usually inactive, precursors. The gene sequences encoding many peptides are now known. Although these indicate the primary structure of the precursor, it remains necessary to define the actual peptide products of cells expressing a particular gene. In several instances, e.g., calcitonin gene-related peptide and preprotachykinin, it is known that there are alternative mRNA splicing mechanisms that generate different precursor molecules. Post-translational processing converts the precursor to smaller active products by cleavage of the chain and by modification to individual residues. The pathways of post-translational processing of the precursors may conveniently be studied using immunochemical methods. These allow detection of products that vary in chain length, or are modified by sulphation, phosphorylation, glycosylation, amidation, or N-terminal acetylation. Patterns of post-translational processing are commonly different between cells expressing the same gene. There are frequently, therefore, multiple active products that can be generated from a precursor, both within a single cell and in different cells expressing the same regulatory peptide gene. Examples are given to indicate the physiologic importance of these mechanisms and how they can be studied.