C 6 glioma and C 2 C 12 satellite cells and their role in cellular signalling

Macula densa cells are located within the thick ascending limb and have their basolateral membrane in contact with its own glomerular mesangial cells, which, in turn, are direct contact with smooth muscle cells of afferent arteriole. Macula densa and mesangial cells are involved in an intrinsing renal mechanism that stabilises glomerular filtration rate at the 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] macula densa cells release increasing amounts of ATP across the basolateral membrane. Once released outside these cells ATP is signaling via the extraglomerular mesangial and smooth muscle cells which posses P2 receptors. Glomerulus cells contains active ecto-nucleotidases that are able to degrade of ATP and terminate ATP signaling.ATP degradation leads to the formation of adenosine and that P1 receptors activation can also plays a role in TGF signaling. The release of ATP via channels and the presence of ecto-nucleotidases provide for a rapid local signaling process with fast on/off kinetics. It should be emphasised 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. On the basis of the avaiable data and their interpretation, we have suggested the TGF vasoconstictor responses do not occur only at the afferent arteriole but there may be involvement of intraglomerular elements that can modify glomerular capillary filtration and its volume.