title: Large variations in the proteolytic formation of a chromogranin A-derived peptide (GE-25) in neuroendocrine tissues.
abstract: 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-filtration HPLC was used to characterize the molecular sizes of the immunoreactive molecules. The antiserum recognized not only the free peptide 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 pituitary gland, intestinal mucosa, pancreas and various brain regions. In adrenal medulla and parathyroid gland most of the immunoreactivity was found to be present as intact chromogranin A and some intermediate-sized peptides, without significant amounts of the free peptide. In anterior pituitary, and even more so in intestine, a shift to smaller peptides was seen. In the posterior and intermediate pituitary and in pancreas the predominant immunoreactive material was apparently represented by the free peptide GE-25. In reverse-phase chromatography this peptide eluted exactly like the synthetic standard, which allows a tentative identification as GE-25. In brain tissue the processing of chromogranin A was intermediate, with significant amounts of immunoreactivity corresponding to GE-25 as well as precursor proteins being present. We suggest that in those organs (endocrine pancreas, intermediate and posterior pituitary) where the major hormones are proteolytically processed there is also a concomitant proteolysis of further susceptible peptides. Since GE-25 is apparently formed in vivo and is well conserved between species it seems a good candidate for having specific physiological functions.
authors.affiliation: Department of Pharmacology, University of Innsbruck, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Kirchmair
authors.forename: B
authors.initials: B
authors.lastname: Leitner
authors.forename: R
authors.initials: R
authors.lastname: Fischer-Colbrie
authors.forename: J
authors.initials: J
authors.lastname: Marksteiner
authors.forename: R
authors.initials: R
authors.lastname: Hogue-Angeletti
authors.forename: H
authors.initials: H
authors.lastname: Winkler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009490:Neurosecretory Systems / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; D011498:Protein Precursors; C095187:chromogranin A (367-391)