Characterization and regional distribution of peptides derived from the vasoactive intestinal peptide precursor in the normal human brain.
To study the biosynthetic processing of the precursor for vasoactive intestinal peptide (prepro-VIP) in the human brain, 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 in radioimmunoassays in combination with HPLC to identify and quantify the peptides in regions of the human brain. All five peptides were expressed, but mainly in nonequimolar ratios. In only three regions were the same amounts of VIP and PHM found; in the remaining areas the concentration of PHM was two-thirds that of VIP. The concentrations of prepro-VIP 22-79, prepro-VIP 111-122, and prepro-VIP 156-170 were considerably lower than the corresponding VIP concentrations, and the relative concentration of prepro-VIP 111-122 differed between cortical and subcortical areas. A small proportion of the VIP precursor followed a pathway in which the dibasic conversion site after PHM is not cleaved, as evidenced by the presence of a C-terminally extended form of PHM. Finally, it was found that the C-terminal lysine residue of prepro-VIP is not removed during processing. The findings indicate that differences in the posttranslational processing of prepro-VIP exist in subpopulations of neurons in the human brain.
Department of Clinical Chemistry, Bispebjerg Hospital, Copenhagen, Denmark.
J
J
Fahrenkrug
P C
PC
Emson
D000368:Aged; D000595:Amino Acid Sequence; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007106:Immune Sera; D008969:Molecular Sequence Data; D010451:Peptide PHI / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis*; D011863:Radioimmunoassay; D014660:Vasoactive Intestinal Peptide / Q000032:analysis*
D007106:Immune Sera; D010451:Peptide PHI; D011498:Protein Precursors; D014660:Vasoactive Intestinal Peptide; C055594:preprovasoactive intestinal peptide