EXPRESSION OF PREPRO VIP-DERIVED PEPTIDES IN THE HUMAN GASTROINTESTINAL-TRACT - A BIOCHEMICAL AND IMMUNOCYTOCHEMICAL STUDY

In order to study biosynthetic processing of the precursor for vasoactive intestinal peptide (prepro VIP) in the human gut we have developed antisera against the five functional domains of the precursor molecule: prepro VIP 22-79, peptide histidine methionine (PHM), prepro VIP 111-122, VIP and prepro VIP 156-170. The antisera were used to quantify and characterize VIP-precursor peptides by radioimmunoassay (RIA) together with high-pressure liquid U chromatography (HPLC) and to examine their cellular localization and colocalization by immunocytochemistry. All five peptides were expressed but not in equimolar amounts as expected from the amino acid sequence of the precursor. However, the ratios between them were fairly constant throughout the gastrointestinal tract. The only exceptions were the lower concentrations of PHM and prepro VIP 111-122 in the gastric antrum which could be explained by the presence of PHV (the C-terminally extended form of PHM which includes prepro VIP 111-122) in large concentrations in this region. It was also found that the C-terminal lysine residue of prepro VIP is not removed during processing. Immunocytochemically all preproVIP-derived peptides were shown in neuronal elements. They had a similar distribution throughout the gut suggesting coexistence, a finding which was supported by doublestaining. The findings indicate that differences in the posttranslational processing of prepro VIP exist in subpopulations of neurons in the human gut.