Stimulation of gastric acid secretion by cAMP in a novel α-toxin- permeabilized gland model

Xuebiao Yao, Sherif M. Karam, Marlon Ramilo, Qinfen Rong, Alain Thibodeau, John G. Forte

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34 Citations (Scopus)


It is generally believed that histamine-stimulated gastric acid secretion involves a transient elevation of intracellular Ca2+ and the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) cascade through phosphorylation, whose actions ultimately effect the fusion of H+-K+-adenosinetriphosphatase (ATPase)containing vesicles to the apical plasma membrane of parietal cells. To dissect the signaling events underlying gastric acid secretion, we have developed a permeabilized gastric gland model using Staphylococcus α-toxin. The advantage of this model is its ability to retain cytosolic components that are required for the secretory machinery. Here we show that acid secretion in α-toxin-permeabilized glands is a cAMP- dependent process, reaching a maximal stimulation at 100 μM cAMP. The cAMP- elicited acid secretion, as monitored by the accumulation of the weak base aminopyrine (AP), required functional mitochondria or exogenously supplied ATP. Maximal stimulation elicited by cAMP for AP uptake by permeabilized glands was 51-85% of intact glands. Moreover, secretory activity was potentiated by 0.1 mM ATP. The recruitment of H+-K+-ATPase-rich tubulovesicles into the apical plasma membrane was measured using biochemical and morphological assays, thus validating the cell activation processes in response to cAMP. From this permeabilized model, [γ-32P]ATP was used to directly phosphorylate target proteins. A number of proteins whose phosphorylation-dephosphorylation is specifically modulated by cAMP were found. These studies establish the first permeabilized gland model in which the resting-to-secreting transition can be triggered and show that cAMP- mediated phosphorylation is correlated with secretory activity.

Original languageEnglish
Pages (from-to)C61-C73
JournalAmerican Journal of Physiology - Cell Physiology
Issue number1 40-1
Publication statusPublished - Jul 1996
Externally publishedYes


  • energy metabolism
  • hydrogen-potassium-activated adenosinetriphosphatase
  • membrane recruitment
  • phosphoproteins
  • protein kinase A

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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