Adenosine, type 1 receptors: role in proximal tubule Na+ reabsorption

Adenosine type 1 receptor (A(1)-AR) antagonists induce diuresis and natriuresis in experimental animals and humans. Much of this effect is due to inhibition of A(1)-ARs in the proximal tubule, which is responsible for 60-70% of the reabsorption of filtered Na+ and fluid. Intratubular application of receptor antagonists indicates that A(1)-AR mediates a portion of Na+ uptake in PT and PT cells, via multiple transport systems, including Na+/H+ exchanger-3 (NHE3), Na+/PO4(-) co-transporter and Na+-dependent glucose transporter, SGLT. Renal microperfusion and recollection studies have shown that fluid reabsorption is reduced by A(1)-AR antagonists and is lower in A(1)-AR KO mice, compared to WT mice. Absolute proximal reabsorption (APR) measured by free-flow micropuncture is equivocal, with studies that show either lower APR or similar APR in A(1)-AR KO mice, compared to WT mice. Inhibition of A(1)-ARs lowers elevated blood pressure in models of salt-sensitive hypertension, partially due to their effects in the proximal tubule.