Paracrine factors in tubuloglomerular feedback: adenosine, ATP, and nitric oxide.
The tubuloglomerular feedback response, the change in afferent arteriolar tone caused by a change in NaCl concentration at the macula densa, is likely initiated by the generation of a vasoactive mediator within the confines of the juxtaglomerular apparatus. Substantial progress has been made in identifying the nature of this mediator and the factors that modulate its effect on vascular tone. In support of earlier studies using P1 purinergic antagonists, the application of the knockout technique has shown that adenosine 1 receptors are absolutely required for eliciting TGF responses. The background level of angiotensin II appears to be an important cofactor determining the efficiency of A1AR-induced vasoconstriction, probably through a synergistic interaction at the level of the G protein-dependent transduction mechanism. The source of the adenosine is still unclear, but it is conceivable that adenosine is generated extracellularly from released ATP through a cascade of ecto-nucleotidases. There is also evidence that ATP may activate P2 receptors in preglomerular vessels, which may contribute to autoregulation of renal vascular resistance. Nitric oxide (NO), generated by the neuronal isoform of nitric oxide synthase in macula densa cells, reduces the constrictor effect of adenosine, but the regulation of NO release and its exact role in states of TGF-induced hyperfiltration are still unclear.
Schnermann
Jürgen
J
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1370, USA. jurgens@intra.niddk.nih.gov
Levine
David Z
DZ
D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D025461:Feedback, Physiological / Q000502:physiology; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019899:Paracrine Communication / Q000502:physiology
D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D000241:Adenosine