Metal ion-dependent binding of gastrin to albumin

Abstract

Binding of 125I-[Nle 15]gastrin to albumin purified from porcine serum, from porcine gastric mucosal cytosol, and from bovine serum has been demonstrated by covalent cross-linking and ultracentrifugation. Binding was enhanced in the presence of Zn 2+, Ni 2+, Cu 2+, Co 2+, and Cd 2+, but not Ca 2+, Mg 2+, or Mn 2+. The best fit to the binding data for bovine serum albumin was obtained with a model assuming two nonequivalent binding sites. The affinity of both sites for gastrin was increased in the presence of 100 μ m Zn 2+ or Ni 2+ ions. The highest association constant observed was 2.3 × 10 5 m −1 in the presence of 100 μ m Zn 2+ ions. The similarity of the Zn 2+-dependence of binding for bovine and porcine serum albumins, despite the replacement of His3 by Tyr, suggested that the N-terminal metal ion-binding site was not involved. Although all gastrin affinities were reduced by 50% in the presence of 150 m m NaCl, the Zn 2+-dependence of binding was retained. We therefore propose that the ternary complex of gastrin, Zn 2+ ions, and albumin may play a physiological role in the serum transport of Zn 2+ ions and in the uptake of Zn 2+ ions from the lumen of the gastrointestinal tract.