LARGE VARIATIONS IN THE PROTEOLYTIC FORMATION OF A CHROMOGRANIN A-DERIVED PEPTIDE (GE-25) IN NEUROENDOCRINE TISSUES

We have established a radioimmunoassay for GE-25, a peptide present in the C-terminal end of the primary amino acid sequence of chromogranin A where it is flanked by typical proteolytic cleavage sites. Gel-infi ltration HPLC was used to characterize the molecular sizes of the immu noreactive molecules. The antiserum recognized not only the free pepti de but also larger precursors including the proprotein chromogranin A. The tissues with the highest levels of GE-25 immunoreactivity were in decreasing order: the adrenal medulla, the three lobes of the pituita ry gland, intestinal mucosa, pancreas and various brain regions. In ad renal medulla and parathyroid gland most of the immunoreactivity was f ound to be present as intact chromogranin A and some intermediate-size d peptides, without significant amounts of the free peptide. In anteri or pituitary, and even more so in intestine, a shift to smaller peptid es was seen. In the posterior and intermediate pituitary and in pancre as the predominant immunoreactive material was apparently represented by the free peptide GE-25. In reverse-phase chromatography this peptid e eluted exactly like the synthetic standard, which allows a tentative identification as GE-25. In brain tissue the processing of chromogran in A was intermediate, with significant amounts of immunoreactivity co rresponding to GE-25 as well as precursor proteins being present. We s uggest that in those organs (endocrine pancreas, intermediate and post erior pituitary) where the major hormones are proteolytically processe d there is also a concomitant proteolysis of further susceptible pepti des. Since GE-25 is apparently formed in vivo and is well conserved be tween species it seems a good candidate for having specific physiologi cal functions.