Evidence For Carrier-mediated Transport Research Articles

Xenobiotic transporter expression and function in the human mammary gland

Xenobiotic transport in the mammary gland has tremendous clinical, toxicological and nutritional implications. Mechanisms such as passive diffusion, carrier-mediated transport, and transcytosis mediate xenobiotic transfer into milk. In vivo animal and human studies suggest the functional expression of both xenobiotic and nutrient transporters in the lactating mammary gland and the potential involvement of such systems in the significant accumulation of certain compounds in milk. In vitro cell culture systems provide further evidence for carrier-mediated transport across the lactating mammary epithelium. Additionally, molecular characterization studies indicate the expression of various members of the organic cation transporter, organic anion transporter, organic anion polypeptide transporter, oligopeptide transporter, nucleoside and nucleobase transporter, multidrug resistant transporter, and multidrug resistant-like protein transporter families at the lactating mammary epithelium. The in vivo relevance of the expression of such xenobiotic and nutrient transporters and their involvement in drug disposition at the mammary gland requires investigation.

CO concentration-dependent changes in pulmonary diffusing capacity in humans.

Steady-state CO pulmonary diffusing capacity (DLCO) was measured at different inspired CO concentrations in seven males and one female during light treadmill exercise. As the CO level is increased. DLCO increases, reaches a maximum at an end-tidal CO concentration of approximately 100 ppm, and then decreases. The maximum DLCO is up to twice as large as the DLCO measured at an inspired CO concentration of approximately 1,780 ppm. These results are consistent with the presence of saturation kinetics, one of the basic properties of carrier-mediated transport systems. A similar relationship between DLCO and CO concentration was found in previous studies of mechanically ventilated dogs. Thus there is evidence for carrier-mediated transport of CO in the lungs of both humans and dogs.

Biliary excretion of diethylstilbestrol in the rhesus monkey.

The biliary excretion of diethylstilbestrol in the bile fistula rhesus monkey was investigated during exogenous taurocholate- and taurodehydrocholate-induced choleresis. Following intravenous administration, 36% of the dose was excreted into the bile (as diethylstilbestrol monoglucuronide) and 53% in the urine (as diethylstilbestrol monoglucuronide plus more polar unidentified metabolites). During the steady-state infusion of diethylstilbestrol, with taurocholate-induced choleresis, a bile flow dependent transport for the biliary excretion of diethylstilbestrol monoglucuronide was observed. Evidence for carrier-mediated transport of this metabolite was a bile-to-blood concentration ratio which ranged from 228 to 279 during steady-state experiments. In vitro experiments indicated that diethylstilbestrol monoglucuronide forms an association with taurocholate, as well as the micellar structures of bile, resulting in a severalfold enhancement of solubility above that in aqueous buffer alone. Taurodehydrocholate, a non-micelle-forming bile salt, did not interact with this metabolite and had no effect on its solubility. Substitution of taurodehydrocholate for taurocholate during the steady-state infusion of diethylstilbestrol produced no significant changes in the transport of diethylstilbestrol monoglucuronide from blood to bile.

Evidence for carrier-mediated transport of L-leucine into isolated pea (Pisum sativum L.) chloroplasts

The uptake of leucine into isolated, intact, pea chloroplasts was investigated using the silicone oil centrifugation technique. The internal: external ratio of leucine exceeded unity at low external leucine concentrations. Uptake of leucine at different external concentrations showed passive diffusion and carrier-mediated transport components. Competition for uptake was shown between leucine and isoleucine but not between leucine and glycine. Rates of diffusion of leucine were found to be low compared with glycine, however, fast carrier-mediated transport of leucine assumed more importance at physiological concentrations.