Nh4+ augments net acid secretion by a ouabain-sensitive mechanism
in isolated perfused inner medullary collecting ducts.
Wall, Susan M.
Division of Nephrology, University of Texas Medical School at
Houston, Houston, TX. 77030
APStracts 2:0168F, 1995.
We have shown that NH4+ and K+ compete for extracellular binding on
the Na+-K+-ATPase in the rat terminal inner medullary collecting duct
(tIMCD). The present study explored whether the Na+-K+-ATPase
modulates transepithelial net acid flux (JH+ = total CO2 absorption,
JtCO2 + total ammonia secretion, JtAM). Tubules from the tIMCD were
dissected from deoxycorticosterone (DOC) treated rats and perfused in
vitro. Perfusate and bath were identical physiological saline
solutions containing 25 mM NaHCO3 plus 6 mM NH4Cl, or NH4Cl free.
With NH4+ present, the fall in total CO2 from perfusate to collected
fluid, _tCO2, (2.5 + 0.4 mM, n=6) was accompanied by an increase in
collected total ammonia concentration (0.2 + 0.1 mM). However, in the
absence of NH4Cl, _tCO2 was only 0.9 + 0.2 mM (P < 0.05, n=5).
To determine the mechanism of this NH4Cl-induced increase in net acid
secretion, the effect of Na+-pump inhibition on net acid secretion
was explored. With NH4Cl present JCO2 was 3.8 + 0.5 pmol/mm/min
(ouabain absent) but declined to 1.6 + 0.3 with ouabain addition to
the bath (n=7, P < 0.05). Furthermore, in the presence of NH4Cl,
pHi increased from 7.05 + 0.02 to 7.15 + 0.02 (P < 0.05, n=5)
with ouabain addition and returned to 7.06 + 0.03 (P < 0.05)
with ouabain removal. However, in the absence of NH4Cl, ouabain
failed to reduce JtCO2 (P=NS, n=5) and an increase in pHi was not
observed (n=4, P=NS). In conclusion, NH4+ augments net acid secretion
likely by serving as a proton source for bicarbonate absorption and
titration of other luminal buffers. This ammonium pathway is
dependent on the basolateral membrane Na+-K+-ATPase.
Received 21 June 1995; accepted in final form 11 September 1995.
APS Manuscript Number F199-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95