title: Interactions between intracellular cyclic AMP and agonist-induced inositol phospholipid breakdown in isolated gastric mucosal cells of the rat.
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 [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.
authors.affiliation: Pharmakologisches Institut, Universität, Heidelberg, Federal Republic of Germany.
authors.forename: J
authors.initials: J
authors.lastname: Puurunen
authors.forename: M J
authors.initials: MJ
authors.lastname: Lohse
authors.forename: U
authors.initials: U
authors.lastname: Schwabe
mesh_terms: 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*
chemical_list: 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