A summary of most of these models for renal drug handling of organic cations, organic anions, conjugated drugs and hydrophobic agents, including the proteins representing specific transport mechanisms, is presented graphically in Figure 2. The following sections describe these mechanisms in more detail. For easier conceptualization, the transporter proteins described below are grouped by their location at either the basolateral or apical membrane of renal tubular cells. Specialized transporters are listed based on their location, but are later described in greater detail. buy ampicillin
Transporters at the basolateral membrane
A proton concentration gradient exists between the three compartments involved in renal drug secretion. As indicated in Figure 2, the pHs of urine, renal tubular cells and the ECF are roughly 6.7, 7.2 and 7.4, respectively. Thus, the concentration of protons is greatest in the urine and lowest in the ECF. Furthermore, an electrical gradient is also maintained between the renal tubular lumen (0 mV), renal tubular cell (—70 mV) and blood (—3 mV). As you may recall, the basolat-eral membrane is in contact with the ECF. Electrogenic pH-independent transport systems located here are able to transport organic cations from the ECF into the renal tubular cells. The transporters are believed to be the proteins coded by the OCT1, OCT2 and OCT3 genes. At the brush border membrane is a proposed electroneutral pH-dependent hydrogen/organic cation antiporter system energized by the transmembrane hydrogen gradient that is sustained by an Na+/H+ exchanger and/or hydrogen-ATPase. Thus, organic cation transport is mediated by a variety of transmembrane proteins that either sustain or depend on both a pH and an electrical gradient.