Gastrin and carbachol require cAMP to elicit aminopyrine accumulation in isolated pig and rat parietal cells

Abstract

The role of endogenous adenosine 3',5'-cyclic monophosphate (cAMP) in the mechanisms of action of gastrin and carbachol on aminopyrine accumulation in isolated pig and rat parietal cells was investigated. In pig cells, pentagastrin (100 nM) alone stimulated aminopyrine accumulation, an action significantly reduced by the protein kinase A inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMP[S]; 100 microM). In rat cells, gastrin-17 (100 nM) was incapable of stimulating aminopyrine accumulation, but it potentiated the action of histamine (100 microM). Carbachol (10 microM) stimulated aminopyrine accumulation and potentiated the action of histamine, and its action was potentiated in a dose-dependent manner by Sp-adenosine 3',5'-cyclic monophosphothioate (Sp-cAMP[S]; a cAMP analogue) in both species. The effect of carbachol was dose dependently reduced by Rp-cAMP[S]. The basal cAMP in pig parietal cells was 3.5-fold higher than that in rat parietal cells. Histamine (100 microM) and 3-isobutyl-1-methylxanthine (IBMX; 100 microM) only slightly elevated the cAMP content (1.2- to 2.9-fold the basal level) in both pig and rat parietal cells. Their combination, however, increased the cAMP level by 8- to 38-fold, but it did not increase aminopyrine accumulation above that elicited by histamine alone. Gastrin did not alter the cAMP levels in parietal cells of either of the two species. Both gastrin and carbachol increased cytosolic free Ca2+ in enriched pig and rat parietal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor–deficient mice

“…The potentiation has been thought to reflect interaction of the intracellular signal transduction pathways including the histaminergic cAMP cascade and gastrinergic/cholinergic Ca 2+ -dependent pathway. In vitro studies have demonstrated that a certain level of cAMP in parietal cells may be required for an optimal secretory response to the Ca 2+ -dependent pathway (8,9). Contrary to the above notion, the present finding that cholinergic signaling could normally control the acid secretion in H2R -/-mice indicates that the Ca 2+ -dependent pathway alone can evoke acid secretion without potentiating the H2R-mediated cAMP pathway.…”

“…Taken together with our present data, this leads us to propose that the muscarinic signal functions stimulate acid production, whereas the gastrin signal mainly functions to promote the proliferation of parietal cells. However, it has been reported that gastrin can directly stimulate isolated canine and porcine parietal cells on acid secretion (6)(7)(8). It is so far unclear why exogenously added gastrin could not induce acid secretion in the mutant mice.…”

Crucial Role of Histamine for Regulation of Gastric Acid Secretion Ascertained by Histidine Decarboxylase-Knockout Mice

“…Because H 2 -receptor antagonists inhibit vagus nerve-and gastrin-stimulated gastric secretion, histamine is thought to represent the final mediator of acid secretion (Grossman and Konturek, 1974). In contrast, in vitro studies have demonstrated that both carbachol and gastrin directly stimulate isolated parietal cells to result in acid secretion (Soll, 1980;Pfeiffer et al, 1990;Li et al, 1995). In addition, histamine amplifies parietal cell stimulation by carbachol and gastrin.…”

Effect of Nitric Oxide on Histamine-Induced Cytological Transformations in Parietal Cells in Isolated Human Gastric Glands

“…2+ ] i has been shown to be necessary for the cytological transformation in parietal cells and subsequent gastric acid secretion [7]. However, it was previously observed that an increase in [Ca 2+ ] i alone was not sufficient to induce full parietal cell stimulation and a simultaneous elevation in cAMP was required in order to ensure cellular stimulation [7,20]. Accordingly, we have observed that upon an increase in [Ca 2+ ] i in resting human parietal cells, a redistribution of F-actin and H + /K + -ATPase occurred.…”