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
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
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 tractThe 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
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 regulatorAngiotensin II Stimulates H+-ATPase Activity in Intercalated Cells from Isolated Mouse Connecting Tubules and Cortical Collecting Ducts
Wagner CA, Mohebbi N, Uhlig U, Giebisch GH, Breton S, Brown D, Geibel JP. Angiotensin II Stimulates H+-ATPase Activity in Intercalated Cells from Isolated Mouse Connecting Tubules and Cortical Collecting Ducts. Cellular Physiology And Biochemistry 2011, 28: 513-520. PMID: 22116365, PMCID: PMC3709473, DOI: 10.1159/000335112.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsAnion Transport ProteinsBicarbonatesCell MembraneChloridesColchicineHydrogen-Ion ConcentrationImmunohistochemistryKidney CortexKidney Tubules, CollectingMacrolidesMaleMiceMice, Inbred C57BLReceptors, AngiotensinSaralasinSodiumSulfate TransportersVacuolar Proton-Translocating ATPasesConceptsCNT/CCDAngiotensin IICortical collecting ductsBicarbonate secretionChloride absorptionCollecting ductsType 1 angiotensin II receptorAngiotensin II stimulatesAngiotensin II receptorsAcid-base statusConnecting tubuleATPase activityII receptorsSpecific subtypesNephron segmentsIndependent intracellularAcid extrusionType BSecretionTubulesDuct systemDuctPendrinPresent studyCellsFunctional 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
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
Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction
Geibel J, Sritharan K, Geibel R, Geibel P, Persing JS, Seeger A, Roepke TK, Deichstetter M, Prinz C, Cheng SX, Martin D, Hebert SC. Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 9390-9397. PMID: 16760252, PMCID: PMC1475505, DOI: 10.1073/pnas.0602996103.Peer-Reviewed Original ResearchConceptsCalcium-sensing receptorCholera toxinFluid secretionNet fluid secretionSecretagogue-induced increasesIntestinal fluid transportCaSR agonistsSecretagogue actionUnique therapyCaSR signalingSecretory actionSecretory diarrheaReceptor activationIntestinal tractEpithelial cellsEnterotoxin STaReceptorsCyclic nucleotidesSecretionExtracellular milieuDiverse cellsToxinActivationCellsDiarrhea