AJP - Renal Physiology, Vol 257, Issue 6 1124-F1131, Copyright © 1989 by American Physiological Society
Phorbol myristate acetate inhibits acidification by turtle urinary bladder
M. Graber, P. Devine and T. Dixon
Northport Veterans Administration Medical Center 11768.
The effects of phorbol myristate acetate (PMA) on acid secretion by the
turtle urinary bladder were examined to evaluate the importance of protein
phosphorylation in modulating the distal acidification system. In HCO3-free
PO4 buffer 0.2 mM mucosal PMA inhibited reverse short-circuit current
(RSCC) by 42%. The inhibition of RSCC was dose dependent, and RSCC
approached zero at high concentrations of PMA. PMA also inhibited acid
secretion measured titrimetrically but had no effect on RSCC from bladders
in which proton secretion was selectively inhibited by an adverse pH
gradient or serosal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The
inhibition by PMA was duplicated by 1-oleoyl-2-acetyl-rac-glycerol, but not
by an inactive phorbol ester. The PMA inhibition was much more potent with
mucosal compared with serosal application. The PMA inhibition caused a
significant 0.15 pH unit reduction of carbonic anhydrase (CA) cell
cytoplasmic pH and a change in the CA cell morphology. Unlike the
inhibition of proton transport induced by acetazolamide, the PMA inhibition
was neither reversed nor prevented by sodium azide. We conclude that PMA
decreases basal acid secretion and blocks the stimulatory effects of CO2 by
an azide-insensitive mechanism distinct from that of acetazolamide. In view
of recent findings that PMA stimulates HCO3 secretion by the turtle
bladder, these results suggest that kinase C-mediated protein
phosphorylation may be a central event in the transition from the secretion
of acid to the secretion of base.
