Driving force for peptide transport in mammalian intestine and kidney

Transport of small intact peptides across the brush-border membrane of the epithelial cells of small intestine and renal proximal tubule is a well-established phenomenon. This peptide transport system recognizes dipeptides and tripeptides as substrates and it is distinct from the transport systems available for absorption of free amino acids. While there is no doubt that active transport of amino acids is energized by a Na+ gradient, the nature of the driving force that energizes peptide transport has been a subject of controversy for many years. Numerous studies with intact tissue preparations have shown that the dependence of peptide transport on a Na+ gradient is at best partial. Recent investigations with isolated brush-border membrane vesicles from small intestine and kidney have clearly established that a H+ gradient rather than a Na+ gradient drives the active transport of intact peptides in these tissues. Since the transport mechanism involves peptide-H+ cotransport, thus rendering the process electrogenic, a membrane potential also plays a role in the energization of this transport system. Nutrient transport driven by an electrochemical H+ gradient is of common occurrence in microorganisms, but peptide transport represents the first example of this kind in mammalian systems. There is strong evidence that a H+ gradient actually exists in vivo across the brush-border membrane of intestinal and renal epithelial cells. The activity of the Na+-H+ exchanger which is located predominantly in the brush-border membrane and which, under physiological conditions, couples the influx of Na+ into the cell with the efflux of H+ from the cell, is primarily responsible for the existence of this H+ gradient. The driving force for the exchanger, a transmembrane Na+ gradient, is in turn generated and maintained at the expense of metabolic energy by the (Na+-K+) ATPase, which is present in the basal-lateral membrane of these cells. Accordingly, peptide transport in small intestine and kidney can be classified as a tertiary active transport system.