ATP release mechanisms, ATP receptors and purinergic signalling along the nephron.

1. Autocrine and paracrine signalling along the nephron of the kidney has been a widely held hypothesis for several decades. The lumen of the nephron is an ideal autocrine and paracrine signalling microenvironment. Any agonist, filtered at the glomerulus or released in the proximal tubule or other proximal segments, is subsequently trapped in the lumen of the nephron and present to interact with luminal receptors. Similar signalling in the renal interstitium is also possible and likely. Indeed, receptors for many autocrine and paracrine agonists have been characterized on the luminal membrane and serosal membrane of multiple nephron segments. 2. An important family of autocrine and paracrine agonists in the kidney are the purinergic agonists. Extracellular ATP, as well as its metabolites (ADP, 5'-AMP and adenosine), is released by renal epithelial cells. These compounds are also freely filtered at the glomerulus and are found in the final urine. Receptors for ATP and adenosine are also expressed on the luminal and serosal side of many nephron segments. 3. The present review discusses purinergic signalling by nucleotide agonists in an integrated manner, from ATP release to ATP receptors to extracellular ATP-mediated effects on renal epithelial function. These themes are the focus of our laboratory in normal and polycystic kidneys as well as in normal and diseased epithelial cells from other tissues. The physiological roles of extracellular purinergic signalling in the kidney and other tissues are only beginning to emerge.