Secretagogue-dependent and -independent transport of zinc hydration forms in rat parietal cells

  • Florentina Sophie Ferstl
  • Alice Miriam Kitay
  • Rebecca Marion Trattnig
  • Abrar Alsaihati
  • John Peter GeibelEmail author
Ion channels, receptors and transporters


Prolonged exposure to gastric acid is a leading cause of gastroesophageal reflux disease (GERD) and esophagitis. With the ever increasing number of patients showing insensitivity to proton-pump-inhibitor (PPI) therapy with recurrence of symptoms over time, alternative treatment options remain an important issue. Previous studies from our laboratory have shown that a zinc sulfate salt can inhibit HCl generation at the cellular level of the parietal cell. In this paper, we examine the difference between two hydration forms of ZnSO4 (monohydrate H2O and heptahydrate 7H2O) in their entry characteristics into the parietal cell under several physiological conditions associated with acid secretion. Using the Zn sensitive fluorochrome Newport Green, we examined the rate of Zn entry in Δfluorescent units/second (ΔFU/second), at two different concentrations for both hydration states on both fasted and non-fasted animals. In a separate series of studies, we examined the effects of secretagogues on the entry rates and transport mechanisms. Exposure of the secretagogue carbachol transformed the resting parietal cell to an activated state and represents a stimulated condition through the neuronal pathway. The hormonal activation of the parietal cell was achieved by using histamine. Non-fasted conditions were considered to be a state between hormonal and neuronal activation. To demonstrate that ZnSO4 enters the parietal cell through the NKCC1 co-transporter, the inhibitor bumetanide was applied during secretagogue-stimulated acid secretion. Both salts, monohydrate and heptahydrate ZnSO4, show a concentration-dependent cell entry under all conditions studied. During stimulated acid secretion, induced through either the neuronal or the hormonal pathway, heptahydrate ZnSO4 enters the parietal cell significantly faster than monohydrate ZnSO4, whereas monohydrate ZnSO4 exhibits faster entry during resting conditions in fasted animals. At 30 μM following stimulation with histamine, heptahydrate ZnSO4 enters the cell faster than monohydrate ZnSO4 (ΔFU/second 30 μM ZnSO4*7H2O + histamine = 1.782, ΔFU/second 30 μM ZnSO4*H2O+histamine = 1.038, respectively). Three hundred micromolar, heptahydrate ZnSO4 shows a faster entry into the cells (ΔFU/second ZnSO4*7H2O300μM + carbachol = 4.02407) compared to monohydrate ZnSO4 (ΔFU/second ZnSO4*H2O300μM + carbachol = 3.225) following exposure to carbachol. The mechanism of entry of both salts was found to be predominantly via the basolateral NKCC1 transporter with the rate of zinc entry decreasing to minimal values (ΔFU/second = 0.275) after application of bumetanide during stimulated conditions.


Stomach Gastric acid secretion NKCC1 co-transporter Bumetanide Newport green 



This work was supported by the Ohse Research Grant Department of Surgery.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Florentina Sophie Ferstl
    • 1
    • 2
  • Alice Miriam Kitay
    • 1
    • 3
  • Rebecca Marion Trattnig
    • 1
    • 2
  • Abrar Alsaihati
    • 1
  • John Peter Geibel
    • 1
    • 4
    Email author
  1. 1.Department of Surgery, School of MedicineYale UniversityNew HavenUSA
  2. 2.Paracelsus Medical UniversitySalzburgAustria
  3. 3.Otto-von-Guericke University MagdeburgMagdeburgGermany
  4. 4.Department of Cellular and Molecular PhysiologyYale University School of MedicineNew HavenUSA

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