Kinetics of zinc absorption by luminally and vascularly perfused rat intestine

Abstract

Zinc absorption by intestines of rats fed either zinc-deficient or zinc-adequate diets was measured by simultaneous luminal and vascular perfusion. The rate of absorption increased steadily for the first 30-40 min of perfusion over the entire lumen zinc concentration range examined (8-234 microM). During the last 10 min of perfusion the absorption rate did not change appreciably with time (steady state), and absorption by intestines from the zinc-depleted rats showed evidence of both carrier-mediated (saturable) and nonmediated (nonsaturable) components. The former had a Km of 55 microM and a Jmax of 3.3 nmol X min-1. In contrast, the absorption rate during the last 10 min of the perfusion period was a sigmoidal function of the luminal zinc concentration with intestines from zinc-adequate rats. The cytosol 65Zn concentration increased proportionately with increased luminal 65Zn concentration but was significantly greater in intestines from zinc-depleted rats. Both high-molecular-weight species and metallothionein accounted for this increase in cytosolic 65Zn. An increase in the vascular bed zinc concentration increased the amount of zinc transferred to the mucosal cytosol but did not increase the amount transferred to the lumen. These results suggest a second mechanism of absorption may be induced during a dietary zinc depletion that is carrier mediated. Moreover, while zinc is transferred in the vascular-to-mucosal direction from the vascular supply, little actually enters the lumen.

Regulation of the zinc transporter ZnT-1 by dietary zinc

“…As a highly charged, hydrophilic ion, Zn(II) cannot cross biological membranes by simple diffusion, and specialized mechanisms therefore must exist for its cellular uptake and release. Zinc absorption has been studied extensively in several model systems, particularly perfused intestinal segments (2,3) and isolated intestinal cells (4). Zinc transport has been characterized in many cell types, including fibroblasts (5), hepatocytes (6,7), placental trophoblasts (8), and endothelial cells (9).…”

<i>In Vitro</i> Study on the Transport of Zinc across Intestinal Epithelial Cells Using Caco-2 Monolayers and Isolated Rat Intestinal Membranes

“…However, detailed information on the intestinal absorption of zinc is likely insufficient at present. Functional studies on the intestinal absorption of zinc using preparations such as everted rat gut sacs, 15,16) the isolated vascularly perfused rat intestine, [17][18][19][20] and intestinal brush-border membrane vesicles from the small intestine of rats 21) provide evidence of saturable components of zinc transport. In most experiments, zinc absorption was measured indirectly.…”

Mammalian Zinc Transporters

“…Experiments with radioisotopes and stable isotopes have identified, through kinetic analysis and metabolic modeling, major pathways by which dietary zinc is processed and how organs in concert produce a fairly effective homeostatic control over absorption and excretion (44,84). Evidence shows reduction in dietary zinc content produces a marked increase in intestinal absorption and decrease in intestinal zinc losses, with urinary losses that are low and refractory to zinc intake (2,32,35,53,63,74,97,98,107). The current dietary recommendations for humans have been based on calculations where zinc intake must balance losses (84).…”

“…At the organ and cellular levels, kinetic studies have shown zinc uptake kinetics exhibit mediated and nonmediated components (74,85,87,89,97). Mediated uptake suggests a saturable mechanism and involvement of a transporter(s).…”