Luminal nucleotides are tonic inhibitors of renal tubular transport

Purpose of review Extracellular ATP is an essential local signaling molecule in all organ systems. In the kidney, purinergic signaling is involved in an array of functions and this review highlights those of relevance for renal tubular transport. Recent findings Purinergic receptors are expressed in all renal tubular segments and their stimulation generally leads to transport inhibition. Recent evidence has identified the tubular lumen as a restricted space for purinergic signaling. The concentrations of ATP in the luminal fluids are sufficiently high to inflict a tonic inhibition of renal tubular absorption via P2 receptors. The apical P2Y(2) receptor plays a crucial role in this process. ATP is released continuously into the tubular lumen. The release is augmented in response to an increase of tubular flow and after stimulation of G-protein-coupled receptors. The primary cilium appears necessary for flow-stimulated luminal ATP release. Tubular ATP secretion may occur via nonjunctional connexin-hemichannels (connexin 30), which are strategically placed in the apical membrane of distal tubular intercalated cells and can be activated by tubular flow. Summary The tubular lumen has been discovered as an important signaling compartment in which local purinergic signaling determines an inhibitory tone for renal tubular transport. Blocking components of this system leads to tubular hyper-absorption, volume retention and elevated blood pressure.