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

Department of Physiology, University of Massachusetts Medical Center Worcester, Massachusetts 01605
Stadtkrankenhaus Neuwied (G.E.F.) , Bonn, West Germany
The Department of Internal Medicine, University Hospital (W.H.H.) CH-8091 Zurich, Switzerland

Address all correspondence and requests for reprints to: Robert E. Carraway, Ph.D., Department of Physiology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts 01605.

An acid extract of a human neuroendocrine pancreatic adenoma was found to contain very high concentrations of immunoreactive neurotensin (iNT; 130 µmol/L) as well as immunoreactive neuromedin-N (iNMN; 40 µmol/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.

^* This work was supported by NIH Grants AM-28565 and AI-19736 and Grant Fe 127/5-7 from the Deutsche Forschungsgemeinschaft.

Received November 5, 1987.