Novel Transporter Responsible for Intestinal Glycerol Absorption : Characterization of Its Function and Physiological Role

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The uptake of glycerol in the everted sacs of the rat small intestine was highly saturable, suggesting the involvement of carrier-mediated transport. Although moderate passive transport component was also observed, it was found that carrier-mediated transport is prevailing at concentrations far lower than the Michaelis constant, where carrier-mediated transport is in the linear phase and most efficient. The glycerol carrier was further suggested to be of Na^+-dependent and secondary active, and specific to glycerol and some analogous compounds. It should also be noted that carrier-mediated glycerol transport is highly efficient, being comparable to D-glucose transport by SGLT1(sodium-dependent glucose transporter 1), which is well known for its very high efficiency. These characteristics of carrier-mediated glycerol transport were consistent with those in the closed loop and the perfused segment of the rat small intestine in situ. Thus, we successfully demonstrated the presence of a carrier-mediated transport system specific to glycerol and some analogous compounds in the rat intestinal tissue, and characterized it kinetically.HCT-15 is a human colon cancer cell line, which was found to be able to perform Na^+-dependent glycerol uptake in the present research project. Although the glycerol carrier in HCT-15 cells was suggested to be different from the one in the small intestine as there was a 50-fold difference in the Michaelis constants, the profiles of inhibition of glycerol transport by various compounds were quite similar, indicating similar characteristics in recognition of substrates and/or inhibitors. Therefore, it maybe possible to use HCT-15 cells for screening inhibitors and potential substrates. HCT-15 could still be a useful model cell line for studies to identify a group of Na^+-dependent glycerol carriers and to elucidate their transport mechanism. Such carriers would be of interest as possible pathways of drug delivery and targets of drug development.