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Regulation of ecto-5'-nucleotidase by NaCl and nitric oxide: potential roles in tubuloglomerular feedback and adaptation

¹Division of Nephrology-Hypertension and ²The Stein Institute for Research on Aging, Department of Medicine, University of California San Diego and Veterans Affairs Medical Center, and ³Department of Medicine and Cancer Center, University of California San Diego, La Jolla, California

Submitted 8 February 2006 ; accepted in final form 15 May 2006

The tubuloglomerular feedback (TGF) system serves to establish an appropriate balance between tubular reabsorption and glomerular filtration rate (GFR). High salt at the macula densa activates TGF to decrease GFR. Effector molecules for the TGF signal include ATP and adenosine. Over time, the GFR will adapt by increasing even if a high salt concentration persists. A potential modulator of this TGF adaptation is nitric oxide synthase-1-derived nitric oxide (NO). In isolated glomerular preparations, we developed a system for evaluating the effects of changing dietary salt on ecto-5'-nucleotidase (ecto-5'-NT) activity, the final enzyme in the conversion of ATP to adenosine. We found observable ecto-5'-NT activity in isolated glomeruli and that this activity can be regulated by dietary salt, with high salt increasing activity. Conversely, NO decreases ecto-5'-NT activity in glomerular preparations. Moreover, NO inhibition of ecto-5'-NT activity is suppressed in the presence of dithiothreitol, suggesting nitrosylation as a reversible, oxidative stress-sensitive mechanism. The salt-induced activation of ecto-5'-NT correlates with high salt resetting of TGF. NO inhibition of enzymatic activity could be part of the adaptive phase.

adenosine; glomerular filtration rate

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