We have been studying the roles of membrane transporter proteins that often significantly affect the pharmacokinetic behavior of drug molecules. The clarification of the functional significance of such transporters will be useful for the mechanistic understanding of interindividual difference in drug activity, the mechanism for pharmacokinetic drug interactions and the development of novel drugs with pharmacokinetically optimized disposition profiles.
Since the drugs are principally xenobiotics for the body, there could be the barrier systems to pump them out for the maintenance of homeostasis. Nevertheless, many types of therapeutic compounds are actually well absorbed through the small intestines. Therefore, we hypothesize the existence of "passport proteins" which accept a certain types of drugs with a passport, enabling them to be absorbed as well as "gateway proteins" which go-between the restriction mechanism(s) for xenobiotics. One of our major projects is to identify the molecular mechanism of these passport and gateway proteins.
Protein-digestive product oligopeptides are absorbed by the specific transporter PEPT1, which is expressed in the intestinal epithelial cells. We demonstrated that PEPT1 is also involved in the oral absorption of several antibacterial agents and angiotensin-converting enzyme inhibitors. We also succeeded to identify OCTN family which acts both as the reabsorption mechanism for carnitine and export mechanism for organic cations in the kidney. We have suggested that the transporters play a crucial role at the blood-brain barrier to maintain homeostasis in the brain. Membrane transporters are thus exciting targets that lead to the rational design of drug molecules, ideal dosage regimen and clarification of biological systems.
to Top page