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 22Na relative to that of [14C]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 22Na reabsorption was modest, the poorly hydrolysable, broad-spectrum P2 agonist ATPgammaS had no significant effect on the Na/inulin recovery ratio. In contrast, in rats maintained on a low-sodium diet, in which amiloride-sensitive 22Na reabsorption was considerably enhanced, ATPgammaS caused a significant increase in the Na/inulin recovery ratio (control: 14 +/- 3%; ATPgammaS: 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 ATPgammaS. The P2Y1 agonist 2meSADP, the P2Y2/4 agonists Ap4A 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.
Shirley
D G
DG
Dept. of Physiology and Centre for Nephrology, Royal Free and Univ. College Medical School, Hampstead Campus, Rowland Hill St., London NW3 2PF, UK. david.shirley@ucl.ac.uk
Bailey
M A
MA
Unwin
R J
RJ
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000345:Affinity Labels / Q000494:pharmacology; D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D004039:Diet, Sodium-Restricted; D053503:Epithelial Sodium Channels; D007685:Kidney Tubules, Collecting / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D009399:Nephrons / Q000166:cytology / Q000378:metabolism; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D012964:Sodium / Q000652:urine*; D015222:Sodium Channels / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000493:pharmacokinetics / Q000652:urine; D012979:Sodium Radioisotopes / Q000493:pharmacokinetics
D000345:Affinity Labels; D053503:Epithelial Sodium Channels; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D015222:Sodium Channels; D017673:Sodium Chloride, Dietary; D012979:Sodium Radioisotopes; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D012964:Sodium