Luminal adenosine receptors regulate amiloride-sensitive, na+
channels in a6 distal nephron cells.
Ma, Heping, and Brian N. Ling.
RENAL DIVISION AND THE CENTER FOR CELL AND MOLECULAR SIGNALING,
DEPARTMENT OF MEDICINE, EMORY UNIVERSITY SCHOOL OF MEDICINE AND
VETERANS AFFAIRS MEDICAL CENTER, ATLANTA, GEORGIA 30322
APStracts 2:0209F, 1995.
To investigate the effects of luminal adenosine on amiloride-sensitive
Na+ channels, we applied the cell-attached patch-clamp technique to
A6 distal nephron cells. Exposure to luminal 30 nM adenosine,
increased NPo (number of channels times the open probability) from
0.38 +/- 0.08 to 0.77 +/- 0.09 (mean +/- SE; P < 0.01; n=17).
Luminal exposure to an A1 receptor antagonist (30 nM DPCPX) abolished
(P = 0.17; n=11), while an A1 agonist (30 nM CHA) reproduced (P
< 0.02; n=6), the stimulatory effect of 30 nM adenosine. In
contrast, higher concentrations of luminal adenosine (1 [mu]M or 10
[mu]M) decreased NPo from 0.65 +/- 0.09 to 0.24 +/- 0.10 (P <
0.02; n=11) and from 0.80 +/- 0.11 to 0.19 +/- 0.03 (P < 0.01;
n=8), respectively. Channel inhibition by high dose luminal adenosine
was abolished by an A2 antagonist (30 [mu]M DMPX) (P = 0.2; n=10),
and mimicked by an A2 agonist (100 nM CGS) (P < 0.0005; n=8).
Conclusions: 1) Purinergic regulation of distal nephron Na+ channels
is mediated by stimulatory, apical A1 receptors and inhibitory apical
A2 receptors. 2) Basal urinary adenosine concentrations (nM) would
stimulate Na+ reabsorption, while higher urinary concentrations
([mu]M) (eg., renal ischemia and elevations in filtered NaCl load)
would increase Na+ excretion. 3) Urinary adenosine may be involved in
feedback regulation of distal nephron Na+ transport.
Received 26 May 1995; accepted in final form 27 November 1995.
APS Manuscript Number F168-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95