Purinergic Signaling in the Juxtaglomerular Apparatus:

In the juxtaglomerular apparatus (JGA) of the kidney the loop of Henle gets into close contact to its parent glomerulus. This anatomical link between the tubular system and the vasculature of the afferent and efferent arteriole enables specialized tubular cells, the macula densa (MD) cells, to establish an intra-nephron feedback loop designed to control both pre-glomerular resistance (and by that single nephron GFR) and renin secretion from granular cells of the afferent arteriole. This review focuses on the signaling mechanisms, which link salt sensing MD cells and the regulation of pre-glomerular resistance, a feedback loop, known as tubuloglomerular feedback (TGF).

The initial step of the TGF is the detection of the NaCl concentration in the tubular lumen by MD cells. As tubular NaCl concentration increases MD cells initiate a signaling process, which eventually leads to a vasoconstriction of the afferent arteriole and by that to a decrease in single nephron GFR, a protective mechanism against the threat of renal salt loss. In pathologic situations, like acute tubular necrosis, with reduced proximal reabsorption and increased salt delivery to the MD segment this feedback loop was suggested to contribute to the fall in total GFR.

The role of TGF in the physiology and patho-physiology of the kidney nourished the interest in identifying the factor(s), which mediate the constriction of the afferent arteriole upon detection of increased tubular salt concentration by MD cells. A possible mediator of the TGF response is supposed to fulfill two key characteristics; (1) it needs to be generated in a regulated fashion in the JGA and (2) it needs to cause vasoconstriction of the afferent arteriole. Both adenosine and ATP fulfill these prerequisites, and a bunch of experimental evidence has accumulated over the years supporting a role of either one as the mediating factor of TGF.