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
2016
Secretagogue-dependent and -independent transport of zinc hydration forms in rat parietal cells
Ferstl FS, Kitay AM, Trattnig RM, Alsaihati A, Geibel JP. Secretagogue-dependent and -independent transport of zinc hydration forms in rat parietal cells. Pflügers Archiv - European Journal Of Physiology 2016, 468: 1877-1883. PMID: 27757581, DOI: 10.1007/s00424-016-1889-3.Peer-Reviewed Original ResearchConceptsGastroesophageal reflux diseaseAcid secretionParietal cellsSecretagogue-stimulated acid secretionRecurrence of symptomsAlternative treatment optionNumber of patientsNon-fasted conditionsApplication of bumetanideEffects of secretagoguesRat parietal cellsReflux diseaseInhibitor therapyTreatment optionsNon-fasted animalsLeading causeNeuronal activationNKCC1 transporterNeuronal pathwaysGastric acidInhibitor bumetanideSecretagogue carbacholFasted animalsMechanism of entryHormonal activation
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
2013
Gastric Acid, Calcium Absorption, and Their Impact on Bone Health
Kopic S, Geibel JP. Gastric Acid, Calcium Absorption, and Their Impact on Bone Health. Physiological Reviews 2013, 93: 189-268. PMID: 23303909, DOI: 10.1152/physrev.00015.2012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntacidsBone and BonesBone Diseases, MetabolicCalcitoninCalciumGastric AcidGastric MucosaHistamine H2 AntagonistsHomeostasisHumansHydrogen-Ion ConcentrationIntestinal AbsorptionIntestinal MucosaIntestinesParathyroid HormoneProton Pump InhibitorsReceptors, Calcium-SensingSignal TransductionVitamin DConceptsBone healthCalcium absorptionIntestinal calcium absorptionGastric acid secretionSystemic calcium homeostasisAdequate intestinal absorptionGastric acidityCalcium balanceGastric acidAcid secretionIntestinal absorptionCalcium homeostasisNeuroendocrine regulationCalcium uptakePhysiological processesPhysiological basisPotential linkHealthSecretionIntestine
2010
Update on the Mechanisms of Gastric Acid Secretion
Kopic S, Geibel JP. Update on the Mechanisms of Gastric Acid Secretion. Current Gastroenterology Reports 2010, 12: 458-464. PMID: 20821079, DOI: 10.1007/s11894-010-0137-9.Peer-Reviewed Original ResearchZinc 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 onsetEthanol Inhibits Gastric Acid Secretion in Rats Through Increased AMP-Kinase Activity
Kopic S, Corradini S, Sidani S, Murek M, Vardanyan A, Föller M, Ritter M, Geibel JP. Ethanol Inhibits Gastric Acid Secretion in Rats Through Increased AMP-Kinase Activity. Cellular Physiology And Biochemistry 2010, 25: 195-202. PMID: 20110680, DOI: 10.1159/000276553.Peer-Reviewed Original ResearchConceptsGastric acid secretionAcid secretionSecretagogue-induced acid secretionInhibits gastric acid secretionShort-term ethanol exposurePH-sensitive dye BCECFLow-dose ethanolCompound CAMPK inhibitor compound CSpecific AMPK inhibitor compound CEffects of ethanolInhibitor compound CEthanol exposureRat gastric glandsActivation of AMPKInteraction of ethanolRat gastric parietal cellsFluorescence digital imagingGastric parietal cellsAMP kinase activityDye BCECFInhibitory effectSecretionParietal cellsAMPK pathway
2009
Revisiting the parietal cell
Kopic S, Murek M, Geibel JP. Revisiting the parietal cell. American Journal Of Physiology - Cell Physiology 2009, 298: c1-c10. PMID: 19889964, DOI: 10.1152/ajpcell.00478.2009.Peer-Reviewed Original ResearchAMP-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 isoformsPI3 Kinase Dependent Stimulation of Gastric Acid Secretion by Dexamethasone
Lang P, Schniepp R, Kirchhoff P, Socrates T, Sidani S, Geibel J. PI3 Kinase Dependent Stimulation of Gastric Acid Secretion by Dexamethasone. Cellular Physiology And Biochemistry 2007, 20: 527-534. PMID: 17762179, DOI: 10.1159/000107536.Peer-Reviewed Original ResearchMeSH KeywordsAndrostadienesAnimalsCimetidineDexamethasoneGastric AcidGastric MucosaH(+)-K(+)-Exchanging ATPaseMaleNitrobenzoatesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPotassium Channel BlockersProtein Kinase InhibitorsProton Pump InhibitorsRatsRats, Sprague-DawleyStaurosporineWortmanninConceptsGastric acid secretionProtein kinase inhibitor staurosporinePI3-kinase inhibitor wortmanninAcid secretionKinase inhibitor staurosporineKinase inhibitor wortmanninPI3-kinase pathwayPeptic ulcerDexamethasone effectApical Cl- channelsKinase pathwayInhibitor wortmanninInhibitor staurosporineExcessive gastric acid secretionProton extrusionATPase inhibitor omeprazoleCl- channel blockers NPPBCl- channelsChannel blocker NPPBDependent stimulationDexamethasone injectionVivo pretreatmentInhibitor omeprazoleParietal cellsSecretion
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 BCECFSecretionThe KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion*
Roepke TK, Anantharam A, Kirchhoff P, Busque SM, Young JB, Geibel JP, Lerner DJ, Abbott GW. The KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion*. Journal Of Biological Chemistry 2006, 281: 23740-23747. PMID: 16754665, DOI: 10.1074/jbc.m604155200.Peer-Reviewed Original ResearchConceptsAncillary subunitsKCNE gene familyGastric acid secretionPotassium channel alpha subunitFirst genetic evidenceSecretory cellsProton secretionChannel alpha subunitGene familyKCNE familyParietal cell morphologyAcid secretionGenetic evidenceAlpha subunitHuman cardiac arrhythmiasParietal cellsChannel complexSubunitsCell morphologyKCNE2Normal gastrointestinal functionGenesKCNQ1Gene-dose effectCellsAn update on acid secretion
Geibel JP, Wagner C. An update on acid secretion. Reviews Of Physiology, Biochemistry And Pharmacology 2006, 156: 45-60. PMID: 16634146, DOI: 10.1007/s10254-005-0003-0.Peer-Reviewed Original ResearchConceptsApical proteinsSecretory pathwayRegulatory mechanismsTransporter proteinsCalcium-sensing receptor activationParietal cellsApical surfaceCalcium-sensing receptorComplex processParietal cell canaliculiAcid productionProteinApical channelsReceptor activationInsertion of pumpsPathwayCellsActivationRecent candidateSecretion of acidSecretionReceptorsAcid secretionCatalytic cycleATPase
2005
An amino acid transporter involved in gastric acid secretion
Kirchhoff P, Dave MH, Remy C, Kosiek O, Busque SM, Dufner M, Geibel JP, Verrey F, Wagner CA. An amino acid transporter involved in gastric acid secretion. Pflügers Archiv - European Journal Of Physiology 2005, 451: 738-748. PMID: 16308696, DOI: 10.1007/s00424-005-1507-2.Peer-Reviewed Original ResearchConceptsAmino acid transportersAcid transportersAmino acidsHeteromeric amino acid transportersHeterodimeric amino acid transportersGastric acid secretionSystem L amino acid transportProtein-rich dietSystem L amino acid transportersSystem L aminoL amino acid transportersAmino acid transportParietal cellsAcid secretionPresence of glutamineNovel roleAcid transportVariety of stimuliIsolated rat gastric glandsTransportersATPase activityNon-metabolizable substratesSystem L.Serum amino acidsGlutamineThe 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