Regulation of Gastric Acid Secretion by PKB/Akt2

Rotte, Anand; Pasham, Venkanna; Bhandaru, Madhuri; Eichenmüller, Melanie; Yang, Wenting; Qadri, Syed M.; Kempe, Daniela S.; Puchchakayala, Goverdhan; Pearce, David; Birnbaum, Morris J.; Läng, Florian

doi:10.1159/000315089

Cited by 12 publications

(15 citation statements)

References 44 publications

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“…DCs were cultured from bone marrow [1,23] of 7-11 weeks old mice lacking functional Akt2/PKBß (akt2 −/− ) and respective wild-type animals (akt2 +/+ ) [7,29]. Prior to the experiments, mice had free access to control diet (1314, Altromin, Heidenau, Germany) and tap drinking water.…”

Section: Animalsmentioning

confidence: 99%

“…After loading, the chamber was flushed for 5 min with Ringer's solution to remove any de-esterified dye. The perfusion chamber was mounted on the stage of an inverted microscope (Zeiss Axiovert 135), which was used in the epifluorescence mode with a ×40 oil immersion objective (Zeiss Neoplan, Germany) [27][28][29][30][31]. BCECF was successively excited at 490/10 and 440/10 nm, and the resultant fluorescent signal was monitored at 535/10 nm using an intensified chargecoupled device camera (Proxitronic, Germany) and specialized computer software (Metafluor, USA).…”

Section: Intracellular Phmentioning

confidence: 99%

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Regulation of Na+/H+ exchanger in dendritic cells by Akt2

Bhandaru

Yang

Rotte

et al. 2011

Pflugers Arch - Eur J Physiol

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Dendritic cells (DCs) are antigen-presenting cells decisive in primary immune responses and establishment of immunological memory. They are activated by bacterial lipopolysaccharides (LPS), which lead to activation of Na(+)/H(+) exchanger activity, cell swelling, reactive oxygen species (ROS) formation, and migration. The effects require functional phosphoinositide 3 kinase and are paralleled by Akt phosphorylation. The present study explored the putative involvement of the Akt isoform Akt2. To this end, experiments were performed in DCs isolated from bone marrow of mice lacking functional Akt2/PKBß (akt2 (-/-)) and respective wild-type animals (akt2 (+/+)). Based on BCECF fluorescence, cytosolic pH (pH(i)) was significantly lower in akt2 (-/-) than in akt2 (+/+) DCs. Transient exposure to NH(4)Cl was followed by profound cytosolic acidification in both genotypes. Subsequent re-alkalinization was largely dependent on Na(+) thus reflecting Na(+)/H(+) exchanger activity and was significantly lower in akt2 (-/-) than in akt2 (+/+) DCs. According to forward scatter in FACS analysis, cell volume was significantly lower in akt2 (-/-) than in akt2 (+/+) DCs. Exposure of DCs to LPS led within 4 h to significant increases of Na(+)/H(+) exchanger activity, cell volume, ROS production, and migration in akt2 (+/+) mice, and its effects were significantly blunted in akt2 (-/-) DCs. The present observations disclose a role of Akt2 in the regulation of pH(i), cell volume, ROS production, and migration in dendritic cells.

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Section: Animalsmentioning

confidence: 99%

Section: Intracellular Phmentioning

confidence: 99%

Regulation of Na+/H+ exchanger in dendritic cells by Akt2

Bhandaru

Yang

Rotte

et al. 2011

Pflugers Arch - Eur J Physiol

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“…Moreover, annexin 7 could interfere with signaling stimulating gastric acid secretion. Gastric acid secretion is stimulated by increase of cytosolic Ca 2+ activity and cAMP [43,65,66] as well as by phosphoinositide 3 kinase (PI3K)-dependent signaling [67,68,69,70]. …”

Section: Discussionmentioning

confidence: 99%

Annexin 7 in the Regulation of Gastric Acid Secretion

Pasham

Rotte²,

Mia³

et al. 2013

Cell Physiol Biochem

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Background/Aims: Glucocorticoids enhance gastric acid secretion and inhibit gastric cyclooxygenase, thus downregulating formation of PGE₂, an inhibitor of gastric acid secretion. In erythrocytes, PGE₂ formation is inhibited by annexin 7. The present study thus explored whether annexin 7 participates in the regulation of gastric acid secretion. Methods: Annexin 7 protein expression was determined by Western blotting, cytosolic pH (pHi) of parietal cells utilizing BCECF-fluorescence, and gastric acid secretion by determination of Na⁺-independent pHi recovery from an ammonium pulse (∆pHi/min). Experiments were performed in isolated glands from gene targeted mice lacking annexin 7 (anx7^-/-) and in respective wild type animals (anx7^+/+). Results: Prior to treatment pHi and ∆pHi/min were similar in isolated gastric glands from anx7^-/- and from anx7^+/+ mice. Aspirin (100 µM added to the glands 1 hr prior to the experiment) significantly increased ∆pHi/min to similar values in both genotypes. The administration of dexamethasone (10 µg/g BW subcutaneously for 4 consecutive days prior to the experiments) significantly increased ∆pH/min in anx7^+/+ mice but not in anx7^-/- mice. Following dexamethasone treatment, the luminal pH was significantly lower and the acid content significantly higher in anx7^+/+ mice than in anx7^-/- mice. An increase of extracellular K⁺ concentration to 35 mM (replacing Na⁺/NMDG⁺) significantly increased ∆pHi/min in both genotypes. In neither genotype dexamethasone increased ∆pH/min further in the presence of 35 mM K⁺ or presence of aspirin. Conclusions: Annexin 7 is required for the stimulation of gastric acid secretion by glucocorticoids.

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“…Possibly, the stimulatory effect of increased cytosolic Ca and cAMP [8,29,30], phosphoinositide 3 kinase (PI3K) dependent signaling participates in the regulation of gastric acid secretion [31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Ca2+ Activated K+ Channel Kca3.1 as a Determinant of Gastric Acid Secretion

Rotte

Pasham²,

Mack³

et al. 2011

Cell Physiol Biochem

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The Ca²⁺ activated K⁺ channel K_ca3.1 is expressed in a variety of tissues. In the gastric gland it is expressed in the basolateral cell membrane. To determine the functional significance of K_ca3.1 activity for gastric acid secretion, gastric acid secretion was determined in isolated glands from gene targeted mice lacking functional K_ca3.1 (K_ca3.1^-/-) and from their wild type littermates (K_ca3.1^+/+). According to BCECF-fluorescence cytosolic pH in isolated gastric glands was similar in K_ca3.1^-/- and K_ca3.1^+/+ mice. Na_ca-independent pH recovery (ΔpH/min) following an ammonium pulse, a measure of H_ca/K_ca ATPase activity, was, however, significantly faster in K_ca3.1^-/- than in K_ca3.1^+/+ mice. Accordingly, the luminal pH was significantly lower and the acid content significantly higher in K_ca3.1^-/- than in K_ca3.1^+/+ mice. The abundance of mRNA encoding H_ca/K_ca ATPase and KCNQ1 was similar in both genotypes. Increase of extracellular K_ca concentrations to 35 mM (replacing Na_ca/NMDG) and treatment with histamine (100 µM) significantly increased ΔpH/min to a larger extent in K_ca3.1^+/+ than in K_ca3.1^-/- mice and dissipated the differences between the genotypes. Carbachol (100 µM) increased ΔpH/min in both genotypes but did not abolish the difference between K_ca3.1^-/- and K_ca3.1^+/+ mice. In K_ca3.1^+/+ mice the K_ca3.1 opener DCEBIO (100 µM) did not significantly alter basal ΔpH/min but significantly blunted ΔpH/min in the presence of carbachol. In conclusion, K_ca3.1 activity suppresses carbachol stimulated gastric acid secretion.

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Regulation of Gastric Acid Secretion by PKB/Akt2

Cited by 12 publications

References 44 publications

Regulation of Na+/H+ exchanger in dendritic cells by Akt2

Regulation of Na+/H+ exchanger in dendritic cells by Akt2

Annexin 7 in the Regulation of Gastric Acid Secretion

Ca<sup>2+</sup> Activated K<sup>+</sup> Channel K<sub>ca</sub>3.1 as a Determinant of Gastric Acid Secretion

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