Adenosine formed by 5'-nucleotidase mediates tubuloglomerular feedback.
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 (V(LP))]. TGF efficiency was significantly reduced by blocking A1-receptors. TGF efficiency, TGF range, and the slope of the TGF profile (DeltaSNGFR/DeltaV(LP)) 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.
Thomson
S
S
Department of Medicine, University of California San Diego and San Diego Veterans Affairs Medical Center, San Diego, California, USA. sthomson@ucsd.edu
Bao
D
D
Deng
A
A
Vallon
V
V
D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D005246:Feedback; D007606:Juxtaglomerular Apparatus / Q000502:physiology; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008866:Microsurgery; D008962:Models, Theoretical; D010477:Perfusion; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000502:physiology
D058915:Purinergic P1 Receptor Antagonists; D015720:5'-Nucleotidase; D000241:Adenosine