N-terminal tryptic fragment of big gastrin. Metabolism and failure to influence gastrin 17-evoked acid secretion in humans.

The metabolism and some biological properties of the N-terminal 1-17 sequence of human big gastrin (G-34) were studied during infusion in 5 human volunteers. Radioimmunoassay of the 1-17 fragment in plasma indicated rapid clearance (t1/2, 2.4 min). In doses of 75-1000 pmol X kg-1 X h-1, 1-17 G-34 did not, however, influence basal acid output or G-17-stimulated acid output. Gel filtration of plasma samples taken during the infusion indicated the presence of the 1-17 fragment of G-34, together with three other immunoreactive species. Two of these correspond to N-terminal G-34 immunoreactive forms previously found in human peripheral circulation. A fourth immunoreactive component that eluted late on Sephadex G50 was identified for the first time. This component also occurred in fasting human plasma, where it was the only detectable form of N-terminal G-34 immunoreactivity; its concentration increased during infusion of 1-17 G-34. The identification of this fragment and its concentrations in human circulation after feeding deserves further study. Because the fragments of 1-17 G-34 do not occur in antral extracts, and are not produced when G-34 or its N-terminal fragments are incubated in plasma in vitro, they are presumed to be generated from the 1-17 sequence by the action of peptidases found on capillary walls. The elucidation of the mechanisms involved is essential for an understanding of the metabolic pathways of gastrin.