AJP - Gastrointestinal and Liver Physiology, Vol 256, Issue 1 129-G138, Copyright © 1989 by American Physiological Society
Sites of action of protein kinase C on secretory activity in rat parietal cells
J. F. Hatt and P. J. Hanson
Pharmaceutical Sciences Institute, Aston University, Birmingham, United Kingdom.
Sites at which the calcium-sensitive phospholipid-dependent protein kinase,
protein kinase C, may influence acid secretion have been investigated in
rat isolated parietal cells. In both crude and enriched preparations of
parietal cells incubated in a medium containing 100 mM K+, the activators
of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA) and
1-oleoyl-2-acetyl-glycerol (OAG), produced a dose-dependent stimulation
[half-maximally effective concentration (EC50) values of 1 nM and 70
microM, respectively] of aminopyrine accumulation, an index of the
sequestration of acid in the cell. In a medium containing 4.5 mM K+, and
with no added secretagogues, TPA and OAG did not affect aminopyrine
accumulation. Histamine-stimulated aminopyrine accumulation was inhibited
by TPA [half-maximally effective inhibitory concentration (IC50) of 2.9
nM]. TPA reduced the histamine-stimulation of the adenosine 3',5'-cyclic
monophosphate (cAMP) content of parietal cells (47% inhibition at 100 nM
TPA) but also inhibited aminopyrine accumulation at or distal to
cAMP-dependent protein kinase. Activators of protein kinase C can produce
multiple effects on secretory activity in the rat parietal cell.
