CHROMOGRANIN A(210-301) IS THE MAJOR FORM OF PANCREASTATIN-LIKE MATERIAL IN HUMAN GUT EXTRACTS AND ENDOCRINE TUMORS

A radioimmunoassay of human pancreastatin was developed using a rabbit antiserum that selectively recognized the C-terminal amidated end of the peptide, and it was used for the identification of the molecular f orms of pancreastatin in human gut (stomach, duodenum, small intestine , colon) and endocrine tumor extracts (liver metastasis of a gastrinom a and a medullary carcinoma of thyroid, one nonsecreting pancreatic tu mor, one recurrence of a gut carcinoid, one vipoma and one insulinoma) . In all gut extracts, a gel filtration chromatography revealed the pr esence of three peaks of pancreastatin-like immunoreactivity. The pred ominant form eluted with an apparent molecular weight higher than that of pancreastatin. This form was also predominant in the endocrine tum ors analyzed, except in the insulinoma, where a lower molecular weight form predominated. The high molecular form was further purified from a liver metastasis of a gastrinoma. The pancreastatin-like immunoreact ivity eluted in all the chromatographical systems (reverse-phase, ion exchange) as a single peak that was finally purified to homogeneity an d sequenced. The sequence of the first 29 N-terminal amino acids was o btained unambiguously and corresponded to the sequence 210-238 of chro mogranin A. Considering the selectivity of the assay used for peptide identification, this major form was identified as the fragment 210-301 of chromogranin A, It is likely that the predominant form of pancreas tatin in human gut extracts and noninsular tumors is a 92 amino acid p eptide.