Increased zinc absorption but not secretion in the small intestine of metallothionein-null mice.

Abstract

Metallothionein (MT) has been assigned a role in intestinal Zn absorption and secretion. The influence of MT was investigated in isolated segments of the small intestine from mice lacking the expression of MT I and II genes (MT-/-). To measure Zn absorption, washed 10- to 12-cm segments of the proximal and distal small intestine of MT-/- and control MT+/+ mice were filled with 65Zn as ZnSO4 (10 microg/mL), and the amount of 65Zn appearing in the external buffer was measured over 4 h. To measure Zn secretion, the same procedure was followed using everted gut segments. The 65Zn absorption from the small intestine was significantly greater in MT-/- mice, but only in the absence of albumin. In the proximal small intestine, the inclusion of 2% albumin in the external buffer significantly increased Zn absorption from 6.8% (no albumin) to 13.2% (with albumin) for MT-/-, and from 4.9% (no albumin) to 14.2% (with albumin) for MT+/+. In the distal segment, the respective values, with and without albumin respectively were 9.5% and 15.1% for MT-/- mice and 4.3% and 16.1% for MT+/+ mice. Regarding 65Zn secretion, there was no difference between MT+/+ and MT-/- in either segment. However, the rate of secretion was higher in the proximal small intestine for both genotypes. Although it can be demonstrated that MT limits Zn absorption under controlled conditions in vitro, the ability of albumin to overcome this effect emphasizes the importance of circulating ligands in Zn transport.