The kidney: A BRIEF INTRODUCTION TO DRUG TRANSPORTERS AND RENAL TUBULAR SECRETION OF DRUGS

In simple terms, the term ‘drug transporter’ refers to a protein that affects how drugs get in or out of cells. Oftentimes, secretion or reabsorption of compounds may be against a concentration gradient so ATP must be consumed by ATPases to produce energy needed for the uphill flow. The movement of molecules that requires ATP consumption is refered to as active transport, whereas passive transport is not energy-dependent. Sometimes exchanger proteins are required that replace one ion or atom with another to provide enough substrate to drive cotransport, or to maintain isoelectricity or pH. Cotransporters move two molecules in the same direction across cell membranes. Counter-transporters move two molecules in opposite directions. The sodium/hydrogen (Na+/H+) antiporter is one such transporter that exchanges sodium for hydrogen ions. buy prednisone

It must be remembered that for renal tubular secretion to occur a molecule must first pass from the extracellular fluid (ECF) (blood) into the renal tubular cell, and then from the renal tubular cell into the tubular lumen to be excreted in the urine. Thus two distinct transporters are required: one at the basolateral membrane of the tubular cell to accept molecules from blood and one at the apical (brush border) membrane to mediate the exit of the molecule into the tubular lumen (urine ) (Figure 2).

Figure2An overview of renal drug
Figure 2) Renal tubular secretory mechanisms. sodium/hydrogen (Na+/H+) antiporter. sodium/potassium (Na+/K+) ATPase. Na+-dicarboxylate (a-ketoglutarate [a—KG]) exchanger. Facilitated diffusion system. cMOAT Canalicular multispecific organic anion transporter; ECF Extracellular fluid; GS-X Glutathione conjugate (note bidirectional flow); HC Hydrophobic compound (neutral charge); HC+ Hydrophobic compound (positive charge); MDR multidrug resistance; MRP multidrug resistance associated protein; OA— Organic anion; OATP Organic anion transport protein; OC+ Organic cation; OCT Organic cation transporter; OCTN Organic cation transporter novel-type; Organic cation transport proposed model only for OCTN; P-gp P-glycoprotein

This entry was posted in Kidney and tagged Drug transport; Kidney; P-glycoprotein; Rena drug handling; Transport protein.