Metal ion-dependent binding of gastrin to albumin.
Binding of 125I-[Nle15]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 Zn2+, Ni2+, Cu2+, Co2+, and Cd2+, but not Ca2+, Mg2+, or Mn2+. 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 microM Zn2+ or Ni2+ ions. The highest association constant observed was 2.3 X 10(5) M-1 in the presence of 100 microM Zn2+ 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 mM NaCl, the Zn(2+)-dependence of binding was retained. We therefore propose that the ternary complex of gastrin, Zn2+ ions, and albumin may play a physiological role in the serum transport of Zn2+ ions and in the uptake of Zn2+ ions from the lumen of the gastrointestinal tract.
Mann
R J
RJ
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Victoria, Australia.
Howlett
G J
GJ
Baldwin
G S
GS
D000818:Animals; D001665:Binding Sites; D002413:Cations, Divalent / Q000494:pharmacology; D005753:Gastric Mucosa / Q000737:chemistry; D005755:Gastrins / Q000302:isolation & purification / Q000378:metabolism*; D008670:Metals / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013552:Swine; D014461:Ultracentrifugation; D015032:Zinc / Q000493:pharmacokinetics
D002413:Cations, Divalent; D005755:Gastrins; D008670:Metals; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D015032:Zinc