Kinetic characterization of in vitro lead transport across the rat small intestine. Mechanism of intestinal lead transport

Lead transport through the everted rat small intestine was used as an in vitro model to examine the kinetics and mechanism of gastrointestinal lead absorption. Mucosal-to-serosal lead flux increased nonlinearly with increasing mucosal lead concentrations (0.5-48.3 μm), and an apparent capacity-limited lead flux was observed with intestines of both adult and adolescent rats. Uptake of lead by the adult intestinal tissue, measured at the end of the flux experiments, was also nonlinearly related to mucosal lead concentration. Both intestinal uptake and mucosal-to-serosal flux were reduced by anoxia and by inhibition of glycolysis using fluoride. The data were consistent with a model of lead intestinal transport which included both a carrier-mediated component and passive diffusion. Kinetic parameters for these transport processes were obtained. The relative contribution of passive diffusion to total lead flux increased with increasing lead concentration, but was quantitatively minor (<20%) at all lead concentrations tested. The apparent capacity-limited component of lead flux was not due artifactually to reduced lead solubility in the mucosal solution at high metal concentrations, nor was it due apparently to reduced viability of the intestinal tissue, since lead did not alter 3-O-methylglucose transport over the range of lead concentration used. When the same lead solution was placed on both sides of an everted intestine, net serosal-to-mucosal lead flux was observed at low lead concentrations. It is therefore likely that intestinal lead transport may be bidirectional, similar to calcium transport.