What's this all about?
The treatment of disease with drugs involves many factors. The ability for drugs to reach the infected area is dependent on absorption, distribution, metabolism, and excretion. This ability is only made possible by transport mechanisms in barrier epithelia. Most drugs carry a positive or negative charge in the body, making them slightly polar and hydrophilic. This is important because it keeps the drugs from permeating across various membranes in the body. Due to these characteristics, our bodies need specialized transport elements to ensure the drug can do its job. The transporters allow certain charged molecules to get through barrier membranes, and are thought to be involved with detoxification and drug disposition. Organic anion transporters and organic cation transporters share some substrates, and their interaction with these substrates depends on the pH of the place where the substrate and transporter meet. Two organic anion transporters, Oat1 and Oat3, are present in the kidney and have been identified as contributors to organic anion secretion. The positioning of these two transporters gives them an active role in determining drug exposure.
Separate tests have found inhibitors for Oat1 and Oat3. Profiles of Oat1 and Oat3 have shown that they have partially redundant roles in the kidney .Substrates shared by Oat1 and Oat3 have different affinities for the transporters, resulting in a concentration-dependent interaction inside the body.
To show the role of Oat3 in the body, the scientists assessed the elimination of p-aminohippurate, estrone-3-sulfate, and penicillin G in Oat3 knockout and wildtype mice. Female Oat3 mice showed decreased clearance of estrone-3-sulfate while male and female Oat3 mice showed highly reduced clearance of penicillin G. There were also signs of possible liver dysfunction in the Oat3 mice. This suggests that Oat3 is involved in the elimination and distribution of organic anions in the body. This finding shows the possibility that humans become more susceptible when they possess a non functioning Oat3.
How was it done?
# The methods used for this experiment include what chemicals and materials were used, the animals used for testing, and the controls and experiment process of how to track the effects caused mainly by penicillin G in the kidney. The process tracked the absorption and distribution in the body. With the intention of a longer period of time for the drug, such as penicillin, to be retained.
# The technique used was to block the protein that transfers the drugs into the kidney, leaving the drug in the bloodstream. The method for that is mainly a probenecid injected (blocking the protein carrier) fifteen minutes before the injection of the substrate solution (such as penicillin G or estrone-3-subsrate). The estrone-3-substrate acts as a competitor for the protein carrier. The mice got injections through a vein in their...