Nh4cl activates ae2 anion exchanger in xenopus oocytes at acidic
phi.
Humphreys, Benjamin D., Marina N. Chernova, Lianwei Jiang, Yun Zhang,
and Seth L. Alper.
Departments of Medicine and Cell Biology, Harvard Medical School,
and Molecular Medicine and Renal Units, Beth Israel Hospital, Boston,
MA 02215
APStracts 3:0344C, 1996.
In the course of experiments to define regulation by pHi of the AE2
anion exchanger expressed in Xenopus oocytes, we discovered an
unexpected regulation of AE2 by NH4+. Intracellular acidification
produced by extracellular acidification or produced by equimolar
substitution of NaCl with sodium acetate each inhibited AE2 activity.
In contrast, intracellular acidification by equimolar substitution of
NaCl with NH4Cl activated AE2-associated, trans-anion-dependent,
DIDS-sensitive 36Cl- influx and efflux. Regulation by NH4 was
isoform-specific, as neither erythroid nor kidney AE1 were activated.
AE2 activation was maximal at <5 mM NH4Cl, was not mimicked by
extracellular Kcl, chloroquine or polyamines, and was insensitive to
amiloride, bumetanide, barium, and gadolinium. Whether NH4Cl acts
directly on AE2 or on another target remains to be determined.
Activation of AE2 by NH4+ may serve to sustain Cl-/HCO3- exchange
activity in the presence of acidic pH in renal medulla, colon,
abcesses and other AE2-expressing acidic locales exposed to elevated
[NH4+].
Received 4 September 1996; accepted in final form 17 October
1996.
APS Manuscript Number C513-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996