Presence of Neurotensin and Neuromedin-N Within a Common Precursor from a Human Pancreatic Neuroendocrine Tumor*

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Abstract
An acid extract of a human neuroendocrine pancreatic adenoma was found to contain very high concentrations of immunoreactive neurotensin (iNT; .apprx. 130 .mu.mol/L) as well as immunoreactive neuromedin-N (iNMN; .apprx. 40 .mu.mol/L), portions of which (iNT, 0.2%; iNMN, 30%) were found in large molecular forms. Processing of the large forms could be 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)]. Biochemcial characterizations using gel electrophoresis, isoelectric focusing, and high pressure liquid chromatography indicated the 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.