Adenosine formed by 5′-nucleotidase mediates tubuloglomerular feedback
Scott Thomson, … , Aihua Deng, Volker Vallon
Scott Thomson, … , Aihua Deng, Volker Vallon
Published January 15, 2000
Citation Information: J Clin Invest. 2000;106(2):289-298. https://doi.org/10.1172/JCI8761.
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Article

Adenosine formed by 5′-nucleotidase mediates tubuloglomerular feedback

Abstract

Nephron function is stabilized by tubuloglomerular feedback (TGF). TGF operates within the juxtaglomerular apparatus, sensing changes in tubular flow and eliciting compensatory changes in single nephron GFR (SNGFR). The mediator(s) of TGF remains unconfirmed. One theory is that ATP consumed in active transport by the macula densa leads to formation of adenosine, which causes glomerular vasoconstriction. We performed micropuncture in rats to test this hypothesis. Adenosine activity was manipulated by microperfusing nephrons with adenosine A1 receptor blocker, A1-agonist, or 5′-nucleotidase inhibitor. Effects on TGF were characterized by changes in TGF efficiency (the compensation for small perturbations in tubular flow) and by changes in the maximum range over which TGF can cause SNGFR to change. These data were further applied to generate TGF profiles [SNGFR versus late proximal flow (VLP)]. TGF efficiency was significantly reduced by blocking A1-receptors. TGF efficiency, TGF range, and the slope of the TGF profile (ΔSNGFR/ΔVLP) were all significantly reduced by blocking 5′-nucleotidase. When adenosine activity was clamped by combining 5′-nucleotidase inhibitor with A1-agonist to determine whether TGF requires adenosine to be present or to fluctuate, the TGF slope was reduced by 83%, indicating that adenosine activity must fluctuate for normal TGF to occur and that adenosine is a mediator of TGF.

Authors

Scott Thomson, Dingjiu Bao, Aihua Deng, Volker Vallon

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Figure 6

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TGF curves generated from the present data. Four parameters are required...
TGF curves generated from the present data. Four parameters are required to generate each curve. These include SNGFRmean, ΔSNGFR, VLP at the inflection point, and f1′ at the inflection point. To generate these curves, it was assumed that f1′ is a symmetric sigmoid and that nephrons in the perturbation experiments were operating near the inflection points of their respective TGF curves. All other features of the curves are obtained directly from the present data.