Macula densa cells are located within the thick ascending limb and have their basolateral membrane in contact with glomerular mesangial cells, which, in turn, are in a direct contact with smooth muscle cells of afferent arteriole. Macula densa and mesangial cells are involved in an intrinsing renal mechanism that stabilizes glomerular filtration rate (GFR) at single nephron level, termed tubuloglomerular feedback (TGF). Macula densa cells are able to sense changes in luminal NaCl concentration and to transmit signal that ultimately constricts the afferent arteriole and reduces glomerular filtration rate. It has been shown that increases in luminal [NaCl] induces macula densa cells to release increasing amounts of ATP across the basolateral membrane. Released ATP to extracellular space affects glomerular cells (mesangial and podocytes) and smooth muscle cells which expressed P2 receptors. Glomerular cells expressed also an active ecto-nucleotidases which are able to degrade of ATP and finally to terminate ATP signaling. ATP degradation leads to the formation of adenosine and activation of P1 receptors, which can also play a role in TGF signaling. The release of ATP via channels and the presence of ecto-nucleotidases provide suggestion for a rapid local signaling process with fast on/off kinetics. It should be emphasized that macula densa cells are very rich in mitochondria and express unique low activity of basolateral Na,K-ATPase. It may suggest that high capacity to generate ATP is due to a high turnover of ATP involved in local signaling process. From the other hand metabolic signal from macula cells may affects the tension of glomerular cells. The tension of mesangial cells and podocytes may influence GFR by affecting the glomerular ultrafiltration coefficient, that is, contraction/relaxation of mesangial cells and/or podocytes may lead to decrease/increase in GFR. On the basis of the available data and their interpretation, we have suggested the GFR regulation does not occur only at the afferent arteriole level but may involve the intraglomerular elements that can modify glomerular capillary filtration and its volume.

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