AJP - Renal Physiology, Vol 252, Issue 6 1073-F1079, Copyright © 1987 by American Physiological Society
Phorbol esters inhibit ammoniagenesis and gluconeogenesis in proximal tubular segments
M. C. Chobanian and M. R. Hammerman
To characterize the regulation of ammoniagenesis and gluconeogenesis in
renal proximal tubule, ammonia and glucose productions were measured in
suspensions of canine proximal tubular segments incubated with 10 mM
L-glutamine. Productions were linear functions of time for 120 min and were
decreased as extracellular pH was increased from 7.0 to 7.5 To ascertain
whether activation of protein kinase c affects either process, we incubated
segments with tumor-promoting phorbol esters,
12-O-tetradecanoylphorbol-13-acetate (TPA), or phorbol 12,13-dibutyrate, or
with the inactive phorbol ester 4 alpha-phorbol. Ammoniagenesis and
gluconeogenesis were inhibited by incubation with 10(-6) M of the two
former compounds but not the latter compound. Inhibition of ammoniagenesis
and gluconeogenesis occurred after incubation with as little as 10(-9) M
phorbol 12,13-dibutyrate. Phorbol ester-induced inhibition was observed
under conditions such that extracellular [Na+] was greater than
intracellular [Na+], but not when extracellular [Na+] equaled intracellular
[Na+], and was not observed in the presence of amiloride. Our findings are
consistent with a role for protein kinase c in the control of
ammoniagenesis and gluconeogenesis in proximal tubule. Such control could
be mediated via stimulation of Na+-H+ exchange.
