2020
Hydrogel‐based 3D bioprints repair rat small intestine injuries and integrate into native intestinal tissue
Maina RM, Barahona MJ, Geibel P, Lysyy T, Finotti M, Isaji T, Wengerter B, Mentone S, Dardik A, Geibel JP. Hydrogel‐based 3D bioprints repair rat small intestine injuries and integrate into native intestinal tissue. Journal Of Tissue Engineering And Regenerative Medicine 2020, 15: 129-138. PMID: 33197151, DOI: 10.1002/term.3157.Peer-Reviewed Original ResearchConceptsIntestinal segmentsPost-operative day 7Male Sprague-Dawley ratsMale Wistar ratsSmall intestine injurySprague-Dawley ratsNative intestineBlinded histopathological analysisIntestinal failureStool outputNative intestinal tissueIntestine injuryIntraluminal perfusionRat vascular cellsHistopathological analysisIleocecal junctionWistar ratsIntestinal integrityIntestinal tissueDay 7Small intestineGenetic malformationsNormal activityWeight gainEnterotomyPenicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt
Baratta VM, Norz V, Barahona MJ, Gisinger TM, Mulligan D, Geibel JP. Penicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt. Cellular Physiology And Biochemistry 2020, 54: 1132-1142. PMID: 33175479, PMCID: PMC8095381, DOI: 10.33594/000000305.Peer-Reviewed Original ResearchConceptsRat colonic cryptsColonic cryptsNitric oxideNitric oxide-dependent mechanismPotassium homeostasisArginine methyl esterAmmonium prepulse techniqueIntracellular nitric oxideSodium-free conditionsL-NAMEDiarrheal statesATPase activityBACKGROUND/Presence of NOPenicillin G sodium saltAcute exposureL-arginineSmall intestineIsolated administrationN-nitroHomeostatic conditionsCryptsPrepulse techniqueSignificant reductionNovel mechanism
2019
The calcium‐sensing receptor: A novel target for treatment and prophylaxis of neratinib‐induced diarrhea
Lysyy T, Lalani AS, Olek EA, Diala I, Geibel JP. The calcium‐sensing receptor: A novel target for treatment and prophylaxis of neratinib‐induced diarrhea. Pharmacology Research & Perspectives 2019, 7: e00521. PMID: 31523434, PMCID: PMC6743423, DOI: 10.1002/prp2.521.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsCaSR activationCalcium-sensing receptorDose-dependent mannerFluid secretionRat intestineHER2-positive breast cancerKinase inhibitorsAdverse effectsChemotherapy-associated diarrheaNeratinib-induced diarrheaCommon side effectsIsolated intestinal segmentsPotent therapeutic targetIrreversible panPatients' qualityBreast cancerIntestinal segmentsSide effectsTherapeutic targetDiarrheaPronounced elevationIntraluminal calcium concentrationVivo modelNeratinib
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 glandsAcute Effects of Vitamin C Exposure On Colonic Crypts: Direct Modulation of pH Regulation
Aldajani MM, Vanicek CN, Alhazzaa N, Lysyy T, Agarwal R, Geibel JP. Acute Effects of Vitamin C Exposure On Colonic Crypts: Direct Modulation of pH Regulation. Cellular Physiology And Biochemistry 2017, 44: 377-387. PMID: 29132138, DOI: 10.1159/000484914.Peer-Reviewed Original ResearchConceptsVitamin CColonic cryptsAcute effectsDependent intracellular pH recoveryTumor formationIntracellular pH recoveryNew therapeutic agentsMM vitamin CColorectal cancerDistal colonLeading causeTranscellular passive diffusionBasolateral membraneAcute additionNormal colonic cryptsC exposureNutraceutical agentTherapeutic agentsPH recoveryIntracellular pH changesCancer cellsVitamin C.CryptsLow intracellularTight junctions
2016
Use of Fluorescein Isothiocyanate-Inulin as a Marker for Intestinal Ischemic Injury
AlKukhun A, Caturegli G, Munoz-Abraham AS, Judeeba S, Patron-Lozano R, Morotti R, Rodriguez-Davalos MI, Geibel JP. Use of Fluorescein Isothiocyanate-Inulin as a Marker for Intestinal Ischemic Injury. Journal Of The American College Of Surgeons 2016, 224: 1066-1073. PMID: 28017811, DOI: 10.1016/j.jamcollsurg.2016.12.016.Peer-Reviewed Original ResearchConceptsFluorescein isothiocyanate-inulinIschemic injuryIntestinal ischemiaIntestinal transplantationFluid secretionIntestinal ischemic injuryIntestinal tissue samplesSmall intestine segmentsHEPES-Ringer solutionIntestinal graftMesenteric ischemiaIschemic intestineHistopathologic samplesExperimental armControl armControl intestineIschemic stateBlinded pathologistIschemiaIntestinal lumenIntestinal tissueIntestine segmentsScoring systemFluid shiftsInjurySecretagogue-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
Calcium-sensing receptor 20 years later
Alfadda TI, Saleh AM, Houillier P, Geibel JP. Calcium-sensing receptor 20 years later. American Journal Of Physiology - Cell Physiology 2014, 307: c221-c231. PMID: 24871857, PMCID: PMC4121584, DOI: 10.1152/ajpcell.00139.2014.Peer-Reviewed Original ResearchConceptsCellular ion transport mechanismsG protein-coupled receptor familyProtein-coupled receptor familyEnvironmental cuesExtracellular environmentOrgan physiologyReceptor familySense changesDifferent tissuesCellular levelCalcium-sensing receptorIon transport mechanismsPhysiologyReceptor physiologyAmino acid concentrationsDisease statesReceptorsSystemic physiologyDiversity of locationsReceptor mutationsDifferent organ systemsImportant roleMembersFamilyHomology
2013
Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR
Collaco AM, Geibel P, Lee BS, Geibel JP, Ameen NA. Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR. American Journal Of Physiology - Cell Physiology 2013, 305: c981-c996. PMID: 23986201, PMCID: PMC4109618, DOI: 10.1152/ajpcell.00067.2013.Peer-Reviewed Original ResearchConceptsV-ATPaseCystic fibrosis transmembrane conductance regulator (CFTR) channelV-ATPase complexV-ATPase functionBrush border membraneProton effluxRat Brunner's glandsIntestinal cellsCAMP/PKACaco-2BBe cellsBorder membraneApical domainCoimmunoprecipitation studiesCFTR distributionVacuolar ATPasesSubapical cytoplasmSpecific subunitsCAMP stimulationProton pumpCAMP treatmentEnterocyte brush border membraneSodium-hydrogen exchangerHydrogen exchangerApical membraneCFTRActivation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine
Rogers AC, Huetter L, Hoekstra N, Collins D, Collaco A, Baird AW, Winter DC, Ameen N, Geibel JP, Kopic S. Activation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine. PLOS ONE 2013, 8: e69050. PMID: 23935921, PMCID: PMC3728293, DOI: 10.1371/journal.pone.0069050.Peer-Reviewed Original ResearchConceptsIntestinal chloride secretionCholera toxinChloride secretionPharmacological activationFluid accumulationColonic cryptsSupplemental treatment strategyAcute diarrheal illnessChloride effluxCystic fibrosis transmembrane conductance regulatorExcised intestinal segmentsRat colonic cryptsMurine colonic mucosaMucosal sheetsDiarrheal illnessIntestinal loopsEnterotoxigenic diarrheaColonic mucosaTreatment strategiesIntestinal segmentsUssing chambersAMPK activator AICARMurine intestineTissue levelsMetforminEffect of NSAIDs on Na+/H+ exchanger activity in rat colonic crypts
Roginiel AC, Kohut DL, Kaur S, Saleh AM, Weber T, Geibel P, Singh H, Geibel JP. Effect of NSAIDs on Na+/H+ exchanger activity in rat colonic crypts. American Journal Of Physiology - Cell Physiology 2013, 305: c512-c518. PMID: 23739181, DOI: 10.1152/ajpcell.00303.2012.Peer-Reviewed Original ResearchConceptsRat colonic cryptsExchanger activityNonsteroidal anti-inflammatory drugsUpper GI injuryColonic cryptsLower GI bleedingUse of NSAIDsChronic inflammatory stateLower GI tractUse of suppositoriesEffects of NSAIDsAnti-inflammatory drugsGI injuryNSAIDs aspirinGI bleedingPain reliefRheumatoid diseaseEpithelial erosionsInflammatory stateMyocardial infarctionChronic conditionsMucosal barrierUlcer formationColonic tissueGastrointestinal tractIdentification of Functionally Distinct Na-HCO3 Co-Transporters in Colon
Barmeyer C, Ye JH, Soroka C, Geibel P, Hingsammer LM, Weitgasser L, Atway D, Geibel JP, Binder HJ, Rajendran VM. Identification of Functionally Distinct Na-HCO3 Co-Transporters in Colon. PLOS ONE 2013, 8: e62864. PMID: 23690961, PMCID: PMC3653958, DOI: 10.1371/journal.pone.0062864.Peer-Reviewed Original ResearchConceptsNa-HCO3 cotransportDistal colonProximal colonNBC activityNBC isoformsRat colonColonic epithelial cellsCrypt glandsSensitive transporterHCO3- secretionColonHCO3-dependent mechanismEpithelial cellsSaturable processHOE694Isoform 1Basolateral membraneCotransportPCR analysisNorthern blotDIDSMolecular studiesMolecular identityApparent KiCritical roleThe calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule
Capasso G, Geibel PJ, Damiano S, Jaeger P, Richards WG, Geibel JP. The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule. Kidney International 2013, 84: 277-284. PMID: 23615500, DOI: 10.1038/ki.2013.137.Peer-Reviewed Original ResearchMeSH KeywordsAcid-Base EquilibriumAnimalsCalcimimetic AgentsCalciumHydrogen-Ion ConcentrationIn Vitro TechniquesKidney Tubules, ProximalMaleMiceMice, KnockoutNuclear ProteinsPerfusionPuncturesRatsRats, Sprague-DawleyReceptors, Calcium-SensingReceptors, G-Protein-CoupledSodium-Hydrogen ExchangersTranscription FactorsConceptsProximal tubulesLuminal calcium concentrationFluid reabsorptionAcid secretionKnockout miceCalcium ion concentrationCalcium concentrationRole of CaSRActivation of CaSRCalcium sensing receptorCalcium-sensing receptorMouse proximal tubulesProton secretionSodium-hydrogen exchangerCalcimimetic agentBicarbonate absorptionSensing receptorCaSRFluid absorptionSecretionReabsorptionMiceCalcimimeticsTubulesLuminal membrane
2012
Effect of the AMP-Kinase Modulators AICAR, Metformin and Compound C on Insulin Secretion of INS-1E Rat Insulinoma Cells under Standard Cell Culture Conditions
Langelueddecke C, Jakab M, Ketterl N, Lehner L, Hufnagl C, Schmidt S, Geibel JP, Fuerst J, Ritter M. Effect of the AMP-Kinase Modulators AICAR, Metformin and Compound C on Insulin Secretion of INS-1E Rat Insulinoma Cells under Standard Cell Culture Conditions. Cellular Physiology And Biochemistry 2012, 29: 75-86. PMID: 22415077, DOI: 10.1159/000337589.Peer-Reviewed Original ResearchConceptsAMP-dependent protein kinaseCompound CStandard cell culture conditionsCell culture conditionsINS-1E rat insulinoma cellsAMPK phosphorylationAMPK inhibitor compound CCulture conditionsCell membrane potentialAMPK-independent mechanismCell metabolic stateInhibitor compound CINS-1E cellsMetabolic stateMembrane potentialStimulus-secretion couplingBasal AMPK phosphorylationΒ-cell survivalCell cycle arrestProtein kinaseΒ-cell line INS-1E.Nutrient uptakeAMPK activatorCell cycle distributionInsulin secretion
2011
Hypoxia Inhibits Colonic Ion Transport via Activation of AMP Kinase
Collins D, Kopic S, Bachlechner J, Ritter M, Winter DC, Geibel JP. Hypoxia Inhibits Colonic Ion Transport via Activation of AMP Kinase. Annals Of Surgery 2011, 254: 957-963. PMID: 21562404, DOI: 10.1097/sla.0b013e31821d477f.Peer-Reviewed Original ResearchConceptsCystic fibrosis transmembrane conductance regulatorChloride secretionMucosal hypoxiaAcute hypoxiaColonic electrolyte transportColonic mucosal functionIschemic intestinal injuryElectrogenic chloride secretionColonic ion transportPotential therapeutic targetHuman colonic mucosaIntracellular chloride concentrationRat colonic cryptsEpithelial ion transportFibrosis transmembrane conductance regulatorIschemic colitisIntestinal injuryColonic obstructionInhibition of CFTRMucosal functionAnastomotic failureAcute effectsColonic mucosaAdaptive cellular responseTransmembrane conductance regulatorVacuolar-type H+-ATPase-mediated proton transport in the rat parietal cell
Kopic S, Wagner ME, Griessenauer C, Socrates T, Ritter M, Geibel JP. Vacuolar-type H+-ATPase-mediated proton transport in the rat parietal cell. Pflügers Archiv - European Journal Of Physiology 2011, 463: 419-427. PMID: 22146938, DOI: 10.1007/s00424-011-1060-0.Peer-Reviewed Original ResearchConceptsV-ATPase activityV-ATPaseAcid secretionParietal cellsRat parietal cellsProton pump inhibitor therapyCertain specialized cellsK-ATPaseProton transportVacuolar-type H-ATPaseK-ATPase inhibitionSecretion pathwayTrafficking mechanismsSpecialized cellsMicrotubule networkActive acidificationInhibitor therapyIntracellular organellesK-ATPase activityRat gastric glandsConcanamycin APharmacological inhibitionAcid loadIntracellular alkalinizationAcid breakthroughFunctional role of NHE4 as a pH regulator in rat and human colonic crypts
Arena EA, Longo WE, Roberts KE, Geibel P, Nateqi J, Brandstetter M, Geibel JP. Functional role of NHE4 as a pH regulator in rat and human colonic crypts. American Journal Of Physiology - Cell Physiology 2011, 302: c412-c418. PMID: 22049213, DOI: 10.1152/ajpcell.00163.2011.Peer-Reviewed Original ResearchConceptsHuman colonic cryptsNHE4 activityColonic cryptsElective colon resectionEffects of aldosteroneSprague-Dawley ratsColon resectionRat modelGastrointestinal tractAldosteroneColonic samplesΜM forskolinFluid homeostasisRatsHuman colonHuman specimensCAMP levelsIntracellular pathwaysCryptsNHE4ColonSignificant changesLittle descriptionFunctional roleRecent studiesThe flavonone naringenin inhibits chloride secretion in isolated colonic epithelia
Collins D, Kopic S, Geibel JP, Hogan AM, Medani M, Baird AW, Winter DC. The flavonone naringenin inhibits chloride secretion in isolated colonic epithelia. European Journal Of Pharmacology 2011, 668: 271-277. PMID: 21762688, DOI: 10.1016/j.ejphar.2011.06.052.Peer-Reviewed Original ResearchConceptsHuman colonic mucosaChloride secretionAntisecretory actionColonic mucosaCo-transporter inhibitorsEffect of naringeninIntracellular cAMP generationColonic cell lineAntisecretory effectColonic functionColorectal cancerProtective effectUssing chambersColonic epitheliumSecretory functionCAMP generationInhibitory actionBasolateral NKCC1Human colonRatsSecretionIntracellular acidificationConflicting resultsCell linesMucosa
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