Evidence for common precursors but differential processing of VIP and PHM in VIP-producing tumors

To elucidate the biosynthesis of vasoactive intestinal polypeptide (VIP) and investigate the suggestion that the prepro-VIP contains another peptide designated PHM (the peptide with N-terminal histidine and C-terminal methionine amide) in its sequence, the concentration and molecular forms of immunoreactive VIP and PHM in 14 human VIP producing tumors (VIP-omas) were determined. Elevated quantities of both peptides were found in all tumor extracts but the concentration of PHM did not correlate with that of VIP and the ratio VIP/PHM varied from 0.5 to 8.5. Gel chromatography showed that in addition to peaks corresponding to VIP and PHM, two larger molecular forms with Kd values of 0.31 and 0.36 which displayed both VIP and PHM immunoreactivity were present. While the proportions between the various PHM molecular forms varied considerably, the relative contribution of the VIP immunoreactive peaks was rather constant from tumor to tumor. The molecular pattern was unaffected by protein denaturing with guanidine hydrochloride and cleavage of sulfide bonds with dithiothreitol. The findings indicate that VIP and PHM are co-produced in VIP-omas probably from common larger molecular forms and that differences in the post-translational processing between tissues exist.