Purinergic Signalling

, 5:461 | Cite as

ATP as a mediator of macula densa cell signalling

  • P. Darwin BellEmail author
  • Peter Komlosi
  • Zhi-Ren Zhang
Original Article


Within each nephro-vascular unit, the tubule returns to the vicinity of its own glomerulus. At this site, there are specialised tubular cells, the macula densa cells, which sense changes in tubular fluid composition and transmit information to the glomerular arterioles resulting in alterations in glomerular filtration rate and blood flow. Work over the last few years has characterised the mechanisms that lead to the detection of changes in luminal sodium chloride and osmolality by the macula densa cells. These cells are true “sensor cells” since intracellular ion concentrations and membrane potential reflect the level of luminal sodium chloride concentration. An unresolved question has been the nature of the signalling molecule(s) released by the macula densa cells. Currently, there is evidence that macula densa cells produce nitric oxide via neuronal nitric oxide synthase (nNOS) and prostaglandin E2 (PGE2) through cyclooxygenase 2 (COX 2)-microsomal prostaglandin E synthase (mPGES). However, both of these signalling molecules play a role in modulating or regulating the macula-tubuloglomerular feedback system. Direct macula densa signalling appears to involve the release of ATP across the basolateral membrane through a maxi-anion channel in response to an increase in luminal sodium chloride concentration. ATP that is released by macula densa cells may directly activate P2 receptors on adjacent mesangial cells and afferent arteriolar smooth muscle cells, or the ATP may be converted to adenosine. However, the critical step in signalling would appear to be the regulated release of ATP across the basolateral membrane of macula densa cells.


ATP Macula densa Cell signalling 



This work was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Disease (DK-32032) and by a Scientist Development Award from the American Heart Association and a VA Merit Grant. We thank Ms. Barbara Harris for administrative assistance.


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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • P. Darwin Bell
    • 1
    • 2
    • 3
    Email author
  • Peter Komlosi
    • 1
    • 2
  • Zhi-Ren Zhang
    • 1
    • 2
  1. 1.Department of Medicine, Division of NephrologyChildren’s Research Institute, Medical University of South CarolinaCharlestonUSA
  2. 2.Department of Veterans AffairsRalph H. Johnson VA Medical CenterCharlestonUSA
  3. 3.Division of NephrologyMedical University of South CarolinaCharlestonUSA

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