2019
Induction of Secretagogue Independent Gastric Acid Secretion via a Novel Aspirin-Activated Pathway
Kitay AM, Ferstl FS, Link A, Geibel JP. Induction of Secretagogue Independent Gastric Acid Secretion via a Novel Aspirin-Activated Pathway. Frontiers In Physiology 2019, 10: 1264. PMID: 31649553, PMCID: PMC6795678, DOI: 10.3389/fphys.2019.01264.Peer-Reviewed Original ResearchGastric acid secretionNon-selective NOS inhibitor L-NAMENOS inhibitor L-NAMEInhibitor L-NAMEAcid secretionL-NAMESoluble guanylyl cyclase inhibitor 1HGuanylyl cyclase inhibitor 1HIncreases nitric oxide productionUsage of aspirinGastric glandsPH-sensitive dye BCECF-AMNitric oxide productionVariety of cancersNovel secretagogueBlood clot formationAspirin exposureChronic conditionsMucosal barrierRepetitive dosesUlcer formationAspirin consumptionBasolateral exposureAspirinClot formation
2018
Modulations in extracellular calcium lead to H+-ATPase-dependent acid secretion: a clarification of PPI failure
Kitay AM, Schneebacher MT, Schmitt A, Heschl K, Kopic S, Alfadda T, Alsaihati A, Link A, Geibel J. Modulations in extracellular calcium lead to H+-ATPase-dependent acid secretion: a clarification of PPI failure. AJP Gastrointestinal And Liver Physiology 2018, 315: g36-g42. PMID: 29517927, DOI: 10.1152/ajpgi.00132.2017.Peer-Reviewed Original ResearchConceptsAcid secretionParietal cellsExtracellular calciumGastric parietal cellsProton pump inhibitor exposureExtracellular CaPotassium-free conditionsRecurrent reflux symptomsCalcium sensing receptorGastric acid secretionPPI failurePPI therapyReflux symptomsIsolated gastric glandsInhibitor exposureCalcimimetic R568Pharmacological targetsSensing receptorAbsence of sodiumCalcium concentrationCaSRGastric glandsSecretionATPase activityExcretion pathway
2017
Activation of Secretagogue Independent Gastric Acid Secretion via Endothelial Nitric Oxide Synthase Stimulation in Rats
Kitay AM, Link A, Geibel JP. Activation of Secretagogue Independent Gastric Acid Secretion via Endothelial Nitric Oxide Synthase Stimulation in Rats. Cellular Physiology And Biochemistry 2017, 44: 1606-1615. PMID: 29212068, DOI: 10.1159/000485755.Peer-Reviewed Original ResearchConceptsNitric oxide synthaseGastric acid secretionAcid secretionL-arginineL-NAMENO/sGC/cGMP pathwayNitric oxideSGC/cGMP pathwayParietal cellsNitric oxide synthase stimulationSGC inhibitor ODQL-arginine exposureAcid-related diseasesPossible intracellular mechanismsNovel secretagogueRat parietal cellsIsolated gastric glandsUlcer diseaseOxide synthaseCGMP pathwayImmune functionImportant mediatorIntracellular mechanismsSecretionGastric glands
2014
Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1
Vucic E, Alfadda T, MacGregor GG, Dong K, Wang T, Geibel JP. Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1. Pflügers Archiv - European Journal Of Physiology 2014, 467: 1457-1468. PMID: 25127675, DOI: 10.1007/s00424-014-1593-0.Peer-Reviewed Original ResearchConceptsGastric parietal cellsPotassium channelsParietal cellsΒ-subunitKir1.1 channelsWild-type miceSecretagogue-stimulated gastric acid secretionApical poleGastric glandsLeak pathwayPotential therapeutic targetKir1.1Proton secretionRegulatory characteristicsKv7.1Therapeutic targetATPaseCell numberParietal cell numberCellsNormal gastric acid secretionSecretionInhibitorsAcid secretionMice
2010
Zinc Salts Provide a Novel, Prolonged and Rapid Inhibition of Gastric Acid Secretion
Kirchhoff P, Socrates T, Sidani S, Duffy A, Breidthardt T, Grob C, Viehl CT, Beglinger C, Oertli D, Geibel JP. Zinc Salts Provide a Novel, Prolonged and Rapid Inhibition of Gastric Acid Secretion. The American Journal Of Gastroenterology 2010, 106: 62. PMID: 20736941, DOI: 10.1038/ajg.2010.327.Peer-Reviewed Original ResearchConceptsProton pump inhibitorsGastric acid secretionAcid secretionRat gastric glandsRandomized cross-over studyIntact rat stomachAcid suppression therapyGastric glandsCross-over studyOnset of actionLong-term efficacyReturn of symptomsHealthy human volunteersSecretagogue-induced acid secretionStomach acid secretionProlonged therapySuppression therapyIntragastric pHPump inhibitorsSingle doseWhole stomachLifetime prevalenceRat modelRat stomachFaster onset
2009
AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion
Sidani S, Kopic S, Socrates T, Kirchhoff P, Föller M, Murek M, Capasso A, Geibel JP. AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion. Pflügers Archiv - European Journal Of Physiology 2009, 459: 39. PMID: 19621238, DOI: 10.1007/s00424-009-0698-3.Peer-Reviewed Original ResearchConceptsProtein kinaseAMPK activationSecretagogue-induced acid secretionCellular ATP levelsPresence of AMPKEnergy-dependent transportersImmunofluorescent localizationParietal cellsGastric glandsCellular ATP consumptionGastric parietal cellsCompound CAMPKProton effluxATP consumptionMetabolic stressRate of intracellularATP levelsKinaseAdenosine monophosphateRegulatorATPLarge abundanceCellsActivation
2007
SLC26A7 Can function as a chloride-loading mechanism in parietal cells
Kosiek O, Busque SM, Föller M, Shcheynikov N, Kirchhoff P, Bleich M, Muallem S, Geibel JP. SLC26A7 Can function as a chloride-loading mechanism in parietal cells. Pflügers Archiv - European Journal Of Physiology 2007, 454: 989-998. PMID: 17404755, DOI: 10.1007/s00424-007-0254-y.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAnimalsAntiportersChloride-Bicarbonate AntiportersChloridesFluorescent Antibody TechniqueGastric AcidGastric MucosaImage Processing, Computer-AssistedIn Vitro TechniquesMaleOocytesParietal Cells, GastricPatch-Clamp TechniquesRatsRats, Sprague-DawleySodiumSodium-Potassium-Chloride SymportersSolute Carrier Family 12, Member 2Sulfate TransportersXenopusConceptsParietal cellsXenopus laevis oocyte expression systemRat parietal cellsExpression of SLC26A7Rat gastric glandsAcid secretionOocyte expression systemNKCC inhibitorWestern blotHistamine stimulationPharmacological inhibitorsAcidic pHiGastric glandsDIDS concentrationExchanger AE2Subsequent readditionTransporter activityDisulfonic acidInhibitorsCellsSLC26A7InfluxImmunohistochemistrySecretagoguesUptake systemStimulatory Pathways of the Calcium-Sensing Receptor on Acid Secretion in Freshly Isolated Human Gastric Glands
Remy C, Kirchhoff P, Hafner P, Busque S, Mueller M, Geibel J, Wagner C. Stimulatory Pathways of the Calcium-Sensing Receptor on Acid Secretion in Freshly Isolated Human Gastric Glands. Cellular Physiology And Biochemistry 2007, 19: 33-42. PMID: 17310098, DOI: 10.1159/000099190.Peer-Reviewed Original ResearchConceptsHeterotrimeric G proteinsHuman gastric glandsMAP kinaseGastric parietal cellsATPase activityG proteinsGastric acid secretionERK 1/2 MAP kinaseIndependent PKC isoformsStimulation of CaSRERK1/2 MAP kinasesAcid secretionProtein kinase CPKC-delta isoformParietal cellsStimulatory effectChelator of intracellularActivation of PKCGastric glandsHuman gastric parietal cellsPLC inhibitor U73122Sensitive heterotrimeric G proteinsPD 098059General inhibitorPKC isoformsEthanol inhibits gastric acid secretion in rats through increased AMP‐K activity
Corradini S, Kopic S, Ritter M, Geibel J. Ethanol inhibits gastric acid secretion in rats through increased AMP‐K activity. The FASEB Journal 2007, 21: a1317-a1317. DOI: 10.1096/fasebj.21.6.a1317-c.Peer-Reviewed Original ResearchSecretagogue-induced acid secretionAcid secretionRate of alkalinizationLow-dose ethanol exposureCompound CPH-sensitive dye BCECFLow-dose ethanolGastric acid secretionInhibitor compound CEthanol exposureRat gastric glandsVariety of cellsNH4Cl prepulseRat gastric parietal cellsGastric parietal cellsSecretagogue carbacholPotent modulatorDye BCECFInhibitory effectParietal cellsSecretionGastric glandsAMP kinasePresent studyGland
2006
ΔF508 Mutation Results in Impaired Gastric Acid Secretion*
Sidani SM, Kirchhoff P, Socrates T, Stelter L, Ferreira E, Caputo C, Roberts KE, Bell RL, Egan ME, Geibel JP. ΔF508 Mutation Results in Impaired Gastric Acid Secretion*. Journal Of Biological Chemistry 2006, 282: 6068-6074. PMID: 17178714, DOI: 10.1074/jbc.m608427200.Peer-Reviewed Original ResearchConceptsCystic fibrosis transmembrane conductance regulatorATP-binding cassette (ABC) transportersFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorMouse gastric glandsParietal cellsMultifunctional proteinCFTR proteinRegulatory proteinsTransport proteinsCassette transportersConductance regulatorRegulatory roleApical poleSecretagogue-induced acid secretionGland lumenGastric glandsSulfonylurea receptorProteinImpaired gastric acid secretionK-ATPaseCl(-) secretionImmunofluorescent localizationCl- channelsATP-sensitive potassium channelsCharacteristics of the K+-competitive H+,K+-ATPase inhibitor AZD0865 in isolated rat gastric glands
Kirchhoff P, Andersson K, Socrates T, Sidani S, Kosiek O, Geibel J. Characteristics of the K+-competitive H+,K+-ATPase inhibitor AZD0865 in isolated rat gastric glands. AJP Gastrointestinal And Liver Physiology 2006, 291: g838-g843. PMID: 16798725, DOI: 10.1152/ajpgi.00120.2006.Peer-Reviewed Original ResearchConceptsGastric acid secretionAcid secretionRat gastric glandsPotassium-competitive acid blockerGastric glandsPeptic ulcer diseaseProton pump inhibitor omeprazoleAcid-related diseasesCompetitive acid blockerPresence of omeprazoleLow-dose inhibitorsFree perfusateUlcer diseasePharmacological treatmentAZD0865High success rateAcid blockerLow doseRapid onsetSensitive dye BCECFInhibitor omeprazoleAcid loadOmeprazoleDye BCECFSecretion
2005
The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands
Dufner MM, Kirchhoff P, Remy C, Hafner P, Müller M, Cheng SX, Tang LQ, Hebert SC, Geibel JP, Wagner CA. The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands. AJP Gastrointestinal And Liver Physiology 2005, 289: g1084-g1090. PMID: 16109841, DOI: 10.1152/ajpgi.00571.2004.Peer-Reviewed Original ResearchConceptsHuman gastric glandsHistamine-induced activationGastric acid secretionGastric glandsExtracellular divalent cationsParietal cellsAcid secretionIsolated rat gastric glandsRelease of acetylcholineCalcium-sensing receptorEnterochromaffin-like cellsAbsence of histamineExtracellular divalent cation concentrationFunctional CaSRATPase activityVagus nerveNeuronal pathwaysRat gastric glandsFura-2Human patientsCaSRFluo-4Sustained increaseCalcium measurementsHistaminel-Type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells
Busque SM, Kerstetter JE, Geibel JP, Insogna K. l-Type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells. AJP Gastrointestinal And Liver Physiology 2005, 289: g664-g669. PMID: 15961860, DOI: 10.1152/ajpgi.00096.2005.Peer-Reviewed Original ResearchConceptsCalcium-sensing receptorAbsence of secretagoguesAcid secretionParietal cellsHistamine-2 receptorSystem L amino acid transportGastric acid secretionWhole stomach preparationDose-dependent increaseIndividual parietal cellsStomach preparationRat gastric glandsHEK-293 cellsCaSRL-amino acidsGastric glandsHormonal stimulationATPase activitySecretionPhysiological concentrationsReceptorsSecretagoguesAcid transportAmino acidsSecretory cells
2001
Gap Junctional Channels Regulate Acid Secretion in the Mammalian Gastric Gland
Radebold K, Horakova E, Gloeckner J, Ortega G, Spray D, Vieweger H, Siebert K, Manuelidis L, Geibel J. Gap Junctional Channels Regulate Acid Secretion in the Mammalian Gastric Gland. The Journal Of Membrane Biology 2001, 183: 147-153. PMID: 11696856, DOI: 10.1007/s00232-001-0062-9.Peer-Reviewed Original ResearchConceptsGap junction channelsAdjacent parietal cellsCell communicationJunction channelsFunctional gap junction channelsGap junctional channelsPotential physiological roleLucifer yellow transferGap junctional proteinGastric glandsParietal cellsWestern blot analysisJunctional channelsJunctional proteinsPhysiological roleRapid cellBlot analysisCalcium signalsBasolateral membraneCell microinjectionAcid secretory processTransfer of dyeSecretory processIntact glandsCalcium wave propagationThe Stomach Divalent Ion-sensing Receptor SCAR Is a Modulator of Gastric Acid Secretion*
Geibel J, Wagner C, Caroppo R, Qureshi I, Gloeckner J, Manuelidis L, Kirchhoff P, Radebold K. The Stomach Divalent Ion-sensing Receptor SCAR Is a Modulator of Gastric Acid Secretion*. Journal Of Biological Chemistry 2001, 276: 39549-39552. PMID: 11507103, DOI: 10.1074/jbc.m107315200.Peer-Reviewed Original ResearchConceptsDivalent cation receptorsTransport proteinsPlasma membrane transport proteinsMembrane transport proteinsGastric acid secretionGastric parietal cellsParietal cellsExact functionNovel pathwayGastric glandsReceptor familySecretory cellsAcid secretionCalcium-sensing receptorBasolateral membranePathwayEndocrine pathwaysExtracellular cationsProteinNew insightsATPaseRat gastric glandsRegulationCellsDivalent cations
1999
Expression of an extracellular calcium-sensing receptor in rat stomach
Cheng* ‡, Qureshi§ I, Chattopadhyay‡ N, Qureshi§ A, Butters‡ R, Hall∥ A, Cima* R, Rogers∥ K, Hebert∥ S, Geibel§ J, Brown‡ E, Soybel* D, ¶NPS Pharmaceuticals I. Expression of an extracellular calcium-sensing receptor in rat stomach. Gastroenterology 1999, 116: 118-126. PMID: 9869609, DOI: 10.1016/s0016-5085(99)70235-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBlotting, NorthernCalciumCells, CulturedDNA, ComplementaryExtracellular SpaceGastric MucosaImmunohistochemistryMolecular Sequence DataMuscle, SmoothParietal Cells, GastricRatsRats, Sprague-DawleyReceptors, Calcium-SensingReceptors, Cell SurfaceReverse Transcriptase Polymerase Chain ReactionRNAStomachTranscription, GeneticConceptsGastric glandsExtracellular calcium-sensing receptorEpithelial cellsCalcium-sensing receptorReverse transcription-polymerase chain reactionGastric surface cellsMammalian gastric mucosaExpression of CARMyenteric neuronsSubmucosal plexusSurface cellsGastric functionPolymerase chain reactionNerve regionRat stomachGastric mucosaGlandular stomachExtracellular Ca2Secretory functionRat parathyroidSystemic Ca2AbstractTextLevels of Ca2CAR expressionStomach
1998
Demonstration of gap junctional protein connexin 32 and connexin 26 among parietal cells of mammalian gastric glands
Ortega G, Caroppo R, Rodas E, Qureshi A, Spray D, Gao Y, Geibel J. Demonstration of gap junctional protein connexin 32 and connexin 26 among parietal cells of mammalian gastric glands. Gastroenterology 1998, 114: a1171. DOI: 10.1016/s0016-5085(98)84762-8.Peer-Reviewed Original Research
1997
A Tyrosine-Based Signal Targets H/K-ATPase to a Regulated Compartment and Is Required for the Cessation of Gastric Acid Secretion
Courtois-Coutry N, Roush D, Rajendran V, McCarthy J, Geibel J, Kashgarian M, Caplan M. A Tyrosine-Based Signal Targets H/K-ATPase to a Regulated Compartment and Is Required for the Cessation of Gastric Acid Secretion. Cell 1997, 90: 501-510. PMID: 9267030, DOI: 10.1016/s0092-8674(00)80510-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCOS CellsCytomegalovirusDNA PrimersEndocytosisGastric AcidGastric MucosaH(+)-K(+)-Exchanging ATPaseMacromolecular SubstancesMiceMice, TransgenicMicroscopy, ImmunoelectronMutagenesis, Site-DirectedParietal Cells, GastricPolymerase Chain ReactionPromoter Regions, GeneticRecombinant ProteinsSignal TransductionTransfectionTyrosineConceptsK-ATPase beta subunitTyrosine-based signalsK-ATPaseTyrosine-based endocytosis signalTyrosine residuesBeta subunitIntracellular storage compartmentEndocytosis signalCytoplasmic tailMutant betaRegulated compartmentsSecrete acidResidue sequenceStorage compartmentCell surfaceCell plasmalemmaSubunitsTransgenic miceParietal cellsGastric glandsCompartmentsSecretionAcid secretionReinternalizationPlasmalemma
1995
Gastrin-stimulated changes in Ca2+ concentration in parietal cells depends on adenosine 3′,5′-cyclic monophosphate levels
Geibel J, Abraham R, Modlin I, Sachs G. Gastrin-stimulated changes in Ca2+ concentration in parietal cells depends on adenosine 3′,5′-cyclic monophosphate levels. Gastroenterology 1995, 109: 1060-1067. PMID: 7557070, DOI: 10.1016/0016-5085(95)90563-4.Peer-Reviewed Original ResearchConceptsCyclic monophosphate (cAMP) levelsParietal cellsECL cellsIntracellular calcium concentration ([Ca2+]i) responseMonophosphate levelsECL-cell responseGastric glandsFunction of adenosineGastrin/cholecystokinin B receptorCholecystokinin B receptorCyclic monophosphate (cAMP) pathwayParietal cell functionAddition of gastrinH2 receptor activityEffect of gastrinIsolated gastric glandsSecretory receptorCell responsesGastrinReceptor activityAbstractTextB receptorCell functionIntracellular adenosineAIMS
1994
Unique Permeability Barrier of the Apical Surface of Parietal and Chief Cells in Isolated Perfused Gastric Glands
Boron W, Waisbren S, Modlin I, Geibel J. Unique Permeability Barrier of the Apical Surface of Parietal and Chief Cells in Isolated Perfused Gastric Glands. Journal Of Experimental Biology 1994, 196: 347-360. PMID: 7823033, DOI: 10.1242/jeb.196.1.347.Peer-Reviewed Original Research