AJP - Renal Physiology, Vol 245, Issue 6 726-F734, Copyright © 1983 by American Physiological Society
Modification of carboxyl of Na+ channel inhibits aldosterone action on Na+ transport
J. Kipnowski, C. S. Park and D. D. Fanestil
We investigated the effect of the carboxyl-selective reagent
N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on aldosterone
stimulation of Na+ transport in the urinary bladder of the toad. Na+
transport, measured as the short-circuit current (SCC), was irreversibly
inhibited by EEDQ in a dose- and time-dependent manner prior to addition of
aldosterone. The greater the percentage inhibition by EEDQ (X), the smaller
was the maximal increase of SCC after aldosterone (Y). This relationship
gave the regression equation Y = 128.41 - 1.73X, r = -0.99 (n = 35).
Evidence that the inhibition of SCC produced by EEDQ was limited to effects
at the mucosal membrane was attested by the following: 1) EEDQ did not
alter the stimulation by aldosterone of the osmotic water flow response to
antidiuretic hormone; 2) whereas inhibition of protein synthesis by
cycloheximide prevented this effect of aldosterone; 3) amphotericin B fully
restored SCC previously inhibited by EEDQ to the level produced in tissues
not inhibited by EEDQ; 4) comparison of the effects of amiloride vs. EEDQ
pretreatment on the SCC response to aldosterone and amphotericin B revealed
nearly identical characteristics; 5) in contrast, amphotericin B
stimulation of SCC was limited when Na+ transport was limited by antimycin
A (an inhibitor of energy production) or by ouabain. The findings fail to
provide positive evidence for the hypothesis that aldosterone induces the
synthesis of new Na+ channels but are consistent with hormonal activation
of previously existing but nonfunctioning Na+ channels.
