Abstract
The interactions between putative second effector mechanisms for hydrogen
ion secretion were studied in isolated gastric cell preparations
of the rat containing 60-70% parietal cells. Dibutyryl-cAMP and the
compounds which increased the level of cAMP (histamine plus rolipram
and forskolin plus rolipram) inhibited the carbachol-induced accumulation
of 3Hinositol tris-, bis- and monophosphate. There was both a temporal
and quantitative correlation between the increase in cAMP and the
inhibition of the accumulation of 3Hinositol phosphates. Cimetidine
attenuated the inhibitory effect of histamine on the formation of
3Hinositol phosphates. The enhancement of the accumulation of 3Hinositol
phosphates by various concentrations of carbachol affected neither
the basal nor the histamine-stimulated cAMP levels. In contrast to
dibutyryl-cAMP, dibutyryl-cGMP did not modify the carbachol-induced
formation of 3Hinositol phosphates. The biologically active phorbol
ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), which activates
protein kinase C, inhibited both the basal and carbachol-induced
accumulation of 3Hinositol phosphates. We suggest that the inhibition
of the formation of inositol trisphosphate by the increase in the
intracellular level of cAMP and by the activation of protein kinase
C might be intracellular negative feedback systems which prevent
the overreaction of the acid-secreting parietal cells under the simultaneous
influence of the physiological gastric secretagogues.
Users
Please
log in to take part in the discussion (add own reviews or comments).