In vivo stimulation of apical P2 receptors in collecting ducts: evidence for inhibition of sodium reabsorption

In vitro evidence suggests that intraluminal nucleotides, acting on apical P2 receptors, may influence amiloride-sensitive sodium reabsorption in collecting ducts. The present study has assessed this possibility directly in anesthetized rats, by determining the urinary recovery of Na-22 relative to that of [C-14] inulin (Na/inulin recovery ratio) during in vivo microperfusion of late distal tubules with artificial tubular fluid containing various P2 agonists (all at 1 mM). In animals maintained on a control diet, in which amiloride-sensitive Na-22 reabsorption was modest, the poorly hydrolysable, broad-spectrum P2 agonist ATP gamma S had no significant effect on the Na/inulin recovery ratio. In contrast, in rats maintained on a low-sodium diet, in which amiloride-sensitive Na-22 reabsorption was considerably enhanced, ATP gamma S caused a significant increase in the Na/inulin recovery ratio (control: 14 +/- 3%; ATP gamma S: 28 +/- 4%; n = 32 pairs; P < 0.001, paired t-test). No change in the Na/inulin recovery ratio was seen in time controls (13 +/- 3 vs. 14 +/- 4%; n = 15 pairs). In subsequent experiments in rats maintained on a low-sodium diet, we used more selective agonists in an attempt to identify the receptor subtype responsible for the effect of ATP gamma S. The P2Y(1) agonist 2meSADP, the P2Y(2/4) agonists Ap(4)A and Cp4U, and the P2X agonist BzATP were all without significant effect on the Na/inulin recovery ratio. These findings constitute the first in vivo evidence for a functional role for apical P2 receptors in collecting ducts, but the identity of the receptor subtype(s) involved remains elusive.