Presence of neurotensin and neuromedin-N within a common precursor from a human pancreatic neuroendocrine tumor.
An acid extract of a human neuroendocrine pancreatic adenoma was found to contain very high concentrations of immunoreactive neurotensin (iNT; approximately 130 mumol/L) as well as immunoreactive neuromedin-N (iNMN; approximately 40 mumol/L), portions of which (iNT, 0.2%; iNMN, 30%) were found in large molecular forms. Processing of the large forms could be mimicked by treatment with pepsin, which increased their immunoreactivity 15- to 20-fold (iNT) and 1- to 2-fold (iNMN), liberating a peptide similar to NMN and 2 fragments of NT [primary product, NT-(4-13)]. Biochemical characterizations using gel electrophoresis, isoelectric focusing, and high pressure liquid chromatography indicated that the large forms were highly basic (pI 8.5-9.5) proteins with a mol wt of about 20K (78% of the total), 45K (8%), and 60K (4%). The 20K protein contained iNT and iNMN in a 1:1 ratio, while a slightly smaller species contained only NMN. These results are in agreement with cDNA studies of canine intestinal mRNA, indicating the presence of a 170-amino acid precursor containing 1 copy each of NT and NMN. They further indicate that within this tumor differential processing of precursor occurred, resulting in a NT to NMN ratio of about 3:1, with additional NMN stored in large molecular forms.
D000236:Adenoma / Q000032:analysis / Q000097:blood / Q000378:metabolism; D000328:Adult; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004586:Electrophoresis; D004700:Endocrine System Diseases / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000097:blood / Q000378:metabolism*; D009496:Neurotensin / Q000097:blood / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D010434:Pepsin A / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011863:Radioimmunoassay; D014020:Tissue Extracts / Q000378:metabolism
D010446:Peptide Fragments; D011498:Protein Precursors; D014020:Tissue Extracts; C042090:neuromedin N; D009496:Neurotensin; D010434:Pepsin A