AJP - Renal Physiology, Vol 250, Issue 3 451-F459, Copyright © 1986 by American Physiological Society
Phorbol ester-induced alkalinization of canine renal proximal tubular cells
J. Mellas and M. R. Hammerman
To determine whether exposure of renal proximal tubular cells to
tumor-promoting phorbol esters results in intracellular alkalinization, we
incubated suspensions of proximal tubular segments isolated from dog kidney
with these compounds. Changes in intracellular pH were detected by
measurements of the distribution of [14C]5,5-dimethoxazolidine-2-4-dione
(DMO). Incubations of segments with 10(-6) M of the tumor-promoting phorbol
esters phorbol-12,13-dibutyrate or 12-O-tetradecanoylphorbol-13-acetate
(TPA), under conditions such that extracellular [Na+] greater than
intracellular [Na+], effected intracellular alkalinization detectable
within 1-2 min. Incubation with the inactive phorbol ester 4 alpha-phorbol
did not. Incubation with as little as 10(-10) M phorbol-12,13-dibutyrate
effected intracellular alkalinization. Incubation with 10(-12) M
phorbol-12,13-dibutyrate did not. Alkalinization was not observed under
conditions such that extracellular [Na+] = intracellular [Na+].
Alkalinization could be prevented by inclusion of 10(-3) M amiloride in
incubations. Our findings are consistent with an action of tumor-promoting
phorbol esters to stimulate Na+-H+ exchange across the plasma membrane of
the renal proximal tubular cell. It is possible that the stimulation
reflects a mechanism by which hormones and/or growth factors exert actions
in proximal tubule.
