Interactions between intracellular cyclic AMP and agonist-induced inositol phospholipid breakdown in isolated gastric mucosal cells of the rat.
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 [3H]inositol tris-, bis- and monophosphate. There was both a temporal and quantitative correlation between the increase in cAMP and the inhibition of the accumulation of [3H]inositol phosphates. Cimetidine attenuated the inhibitory effect of histamine on the formation of [3H]inositol phosphates. The enhancement of the accumulation of [3H]inositol 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 [3H]inositol 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 [3H]inositol 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.
Puurunen
J
J
Pharmakologisches Institut, Universität, Heidelberg, Federal Republic of Germany.
Lohse
M J
MJ
Schwabe
U
U
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000502:physiology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D010295:Parietal Cells, Gastric / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D020889:Rolipram; D013403:Sugar Phosphates / Q000378:metabolism*
D007295:Inositol Phosphates; D010703:Phorbol Esters; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D013403:Sugar Phosphates; D005576:Colforsin; D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; D002927:Cimetidine; D006632:Histamine; D002217:Carbachol; D000242:Cyclic AMP; D011493:Protein Kinase C; D020889:Rolipram