Adenosine formed by 5 '-nucleotidase mediates tubuloglomerular feedback

Nephron function is stabilized by tubuloglomerular feedback (TGF). TGF oper ates within the juxtaglomerular apparatus, sensing changes in tubular flow and eliciting compensatory changes in single nephron GFR (SNGFR). The media tor(s) of TGF remains unconfirmed. One theory is that ATP consumed in activ e transport by the macula densa leads to formation of adenosine, which caus es glomerular vasoconstriction. We performed micropuncture in rats to test this hypothesis. Adenosine activity was manipulated by microperfusing nephr ons with adenosine A1 receptor blocker, A1-agonist, or 5'-nucleotidase inhi bitor. 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 fu rther applied to generate TGF profiles [SNGFR versus late proximal flow (V- LP)]. TGF efficiency was significantly reduced by blocking A1-receptors. TG F efficiency, TGF range, and the slope of the TGF profile (Delta SNGFR/Delt a V-LP) were all significantly reduced by blocking 5'-nucleotidase. When ad enosine activity was clamped by combining 5'-nucleotidase inhibitor with A1 -agonist to determine whether TGF requires adenosine to be present or to fl uctuate, the TGF slope was reduced by 83%, indicating that adenosine activi ty must fluctuate for normal TGF to occur and that adenosine is a mediator of TGF.