Tubuloglomerular feedback in the kidney: insights from gene-targeted mice.
The term tubuloglomerular feedback (TGF) refers to a series of events whereby changes in the concentration of Na(+), Cl(-) and K(+) in the distal tubular fluid are sensed by the macula densa and elicit reciprocal changes in nephron filtration rate (SNGFR). Although micropuncture experiments in the rat and studies in the isolated perfused rabbit juxtaglomerular apparatus (JGA) have yielded significant insights into TGF, many aspects, including the signal transduction and modulation in JGA and the role of TGF in physiology and pathophysiology, are still incompletely understood. This is due in part to the lack of selective drugs for inhibiting or activating a given molecule of interest and to the limited accessibility of target structures or molecules. Adaptation of single-nephron methods to gene-targeted mice is a promising approach for gaining further insights into TGF. The gist of the presently available studies in gene-targeted mice that are reviewed here support the concept that (i) adenosine mediates TGF by activation of adenosine A(1) receptors; (ii) that this response is modulated inversely by nitric oxide synthase 1 activity in macula densa and activation of angiotensin II AT(1A) receptors; and (iii) that the TGF-dependent reduction in SNGFR prevents excessive renal fluid and salt loss during primary inhibition of reabsorption upstream from the macula densa.
Vallon
Volker
V
Department of Pharmacology, University of Tübingen, Germany. volker.vallon@uni-tuebingen.de
D000818:Animals; D004195:Disease Models, Animal; D025461:Feedback, Physiological; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout