Some contributions to the chemistry of the gastrointestinal hormones

Twenty-five years ago we described an extraction procedure for porcine secretin in which the intestinal tissue is briefly boiled in water and then extracted with dilute acid at low temperature. Boiling in water, which inactivates proteolytic enzymes, does not extract secretin, and extraction with acid in the cold will minimize cleavage of acid labile peptide structures. This extraction procedure has formed the basis for the isolation not only of secretin but also of cholecystokinin-pancreozymin (CCK) and, in collaboration with other laboratories, of the vasoactive intestinal peptide (VIP), the gastric inhibitory peptide (GIP), and motilin. Recently it has been used for the isolation of an N-terminally extended somatostatin from intestinal tissue, and of a peptide, from both nonantral gastric and intestinal tissues, with gastrin-releasing and probably cholecystokinin-releasing properties. A technique has been worked out permitting the chemical analysis, in certain cases, of polypeptide hormones in the presence of other polypeptides, the polypeptide mixture being exposed to fragmentation conditions known to result in characteristic hormone fragments, which are then extracted and quantitated. The technique can also be useful for the isolation of previously unknown peptides by identifying fragments of such and tracing them back to their peptides of origin.