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1 Centre for Nephrology and Department of Physiology, Royal Free & University College Medical School, London, United Kingdom
* To whom correspondence should be addressed. E-mail: david.shirley{at}ucl.ac.uk.
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 1mM). In
animals maintained on a control diet, in which amiloride-sensitive 22Na reabsorption was
modest, the poorly hydrolysable, broad-spectrum P2 agonist ATP
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 22Na reabsorption was considerably enhanced, ATPS caused a significant
increase in the Na/inulin recovery ratio (control: 14 ± 3 %; ATPS: 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 sub-type
responsible for the effect of ATPS. 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 sub-type(s) involved
remains elusive.
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