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 ResearchMeSH KeywordsAnimalsCalciumDiarrheaDose-Response Relationship, DrugIntestinesMalePerfusionPhenethylaminesPropylaminesQuinolinesRatsReceptors, Calcium-SensingUp-RegulationConceptsTyrosine 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 modelNeratinibDesign and implementation of novel nutraceuticals and derivatives for treating intestinal disorders
Barahona MJ, Baratta V, Ollodart J, Mulligan D, Geibel JP. Design and implementation of novel nutraceuticals and derivatives for treating intestinal disorders. Future Medicinal Chemistry 2019, 11: 847-855. PMID: 30994367, PMCID: PMC8008207, DOI: 10.4155/fmc-2018-0313.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDietary SupplementsGastrointestinal DiseasesHumansIntestinal MucosaModels, MolecularNanoparticlesReceptors, Calcium-SensingConceptsSignificant worldwide disease burdenSpectrum of illnessWorldwide disease burdenIntestinal fluid secretionSystemic side effectsCalcium-sensing receptorNovel therapeutic targetG protein-coupled receptorsSurgical therapyPharmaceutical optionsMucosal integrityDisease burdenIntestinal disordersNutraceutical therapyGastrointestinal diseasesGastrointestinal illnessSide effectsTherapeutic targetFluid secretionIntestinal cellsTherapyAdverse effectsNovel nutraceuticalsCaSRIllness
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
Stomach and Bone
Kitay AM, Geibel JP. Stomach and Bone. Advances In Experimental Medicine And Biology 2017, 1033: 97-131. PMID: 29101653, DOI: 10.1007/978-3-319-66653-2_6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone and BonesCalciumGastric MucosaHomeostasisHumansIntestinal MucosaKidneyParathyroid HormoneReceptors, Calcium-SensingConceptsBone metabolismGastric acid secretionCalcium-sensing receptorVitamin DParathyroid glandsAcid secretionGastrointestinal organsTherapeutic implicationsEndocrine modulatorsCalcium homeostasisDiseaseStomachOrgansMetabolismImportant playersIntermediary organDiverse tissuesDysfunctionCaSRPTHCalcitoninKidneySecretionIntestineReceptors
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 ResearchMeSH KeywordsAnimalsCalciumCalcium SignalingGastric MucosaHumansIntestinal MucosaIntestinesKidneyMiceMutationRatsReceptors, Calcium-SensingRenal Insufficiency, ChronicSkinStomachConceptsCellular 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
The 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 membraneGastric 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 linkHealthSecretionIntestineActivation of the Ca2+-sensing receptor induces deposition of tight junction components to the epithelial cell plasma membrane
Jouret F, Wu J, Hull M, Rajendran V, Mayr B, Schöfl C, Geibel J, Caplan MJ. Activation of the Ca2+-sensing receptor induces deposition of tight junction components to the epithelial cell plasma membrane. Journal Of Cell Science 2013, 126: 5132-5142. PMID: 24013548, PMCID: PMC3828589, DOI: 10.1242/jcs.127555.Peer-Reviewed Original ResearchConceptsTJ assemblyMDCK cellsStable transfectionFunction mutant formZO-1Tight junction components ZO-1G protein-coupled receptorsHuman CaSRCell-cell contactEpithelial cell plasma membranesMadin-Darby canine kidney cellsCell plasma membraneStimulation of CaSRDivalent ion homeostasisCanine kidney cellsTight junctionsJunction-associated proteinsTight junction componentsEndogenous CaSRProtein kinasePlasma membraneIon homeostasisMutant formsChelator BAPTA-AMCell differentiation
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 ResearchThe calcium-sensing receptor.
Geibel JP. The calcium-sensing receptor. Journal Of Nephrology 2010, 23 Suppl 16: s130-5. PMID: 21170870.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumGene Expression Regulation, DevelopmentalHumansKidneyMagnesiumParathyroid GlandsReceptors, Calcium-SensingConceptsCalcium-sensing receptorExtracellular environmentReceptor-targeted drugsThick ascending limbFiltered loadAscending limbNephron segmentsAmino acidsHandling of waterReceptorsImportant roleBasic physiologyImportant memberSalt absorptionRecent studiesDivalent ion concentrationSalinityCalciumIonic absorptionCaSR
2009
The Functions and Roles of the Extracellular Ca2+–Sensing Receptor along the Gastrointestinal Tract
Geibel JP, Hebert SC. The Functions and Roles of the Extracellular Ca2+–Sensing Receptor along the Gastrointestinal Tract. Annual Review Of Physiology 2009, 71: 205-217. PMID: 19575679, DOI: 10.1146/annurev.physiol.010908.163128.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumGastrointestinal TractHomeostasisHumansIntestinal MucosaReceptors, Calcium-SensingConceptsGastrointestinal tractNormal gut physiologyNutrient availabilityDigestion of foodRapid turnoverAmino acidsColonic fluid transportFunctional digestive tractGastric acid secretionCalcium-sensing receptorOrganic nutrientsWater homeostasisEntire gastrointestinal tractPotent targetGut physiologyEpithelial cellsIntestinal epitheliumSecretory diarrheaAcid secretionDigestive tractExtracellular Ca2Colon cancerReceptorsNormal saltFluid secretion
2007
Stimulatory 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 isoforms
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 cellsToxinActivationCellsDiarrheaAn 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 ResearchMeSH KeywordsAnimalsCalciumEnzyme ActivationGastric AcidGastric MucosaH(+)-K(+)-Exchanging ATPaseHumansModels, BiologicalParietal Cells, GastricReceptors, Calcium-SensingConceptsApical proteinsSecretory pathwayRegulatory mechanismsTransporter proteinsCalcium-sensing receptor activationParietal cellsApical surfaceCalcium-sensing receptorComplex processParietal cell canaliculiAcid productionProteinApical channelsReceptor activationInsertion of pumpsPathwayCellsActivationRecent candidateSecretion of acidSecretionReceptorsAcid secretionCatalytic cycleATPaseRole of calcium and other trace elements in the gastrointestinal physiology
Kirchhoff P, Geibel J. Role of calcium and other trace elements in the gastrointestinal physiology. World Journal Of Gastroenterology 2006, 12: 3229-3236. PMID: 16718844, PMCID: PMC4087967, DOI: 10.3748/wjg.v12.i20.3229.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCell DifferentiationCell ProliferationCell Transformation, NeoplasticColonic NeoplasmsHumansIntestinal MucosaIntestinesReceptors, Calcium-SensingStomachTrace ElementsConceptsCell type changesGastrointestinal tractTerrestrial organismsNutrient availabilityIntestinal epithelial cellsCellular behaviorTerminal differentiationExact functionEssential ionsAmino acidsNeuronal functionGastric acid secretionEpithelial cellsEntire gastrointestinal tractAllosteric modifierCaSR expressionRole of calciumElevated extracellularSecretory diarrheaAcid secretionCalcium handlingReceptorsNeoplastic diseaseGastrointestinal physiologyPhysiological effects
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
2004
Functions and roles of the extracellular Ca2+-sensing receptor in the gastrointestinal tract
Hebert SC, Cheng S, Geibel J. Functions and roles of the extracellular Ca2+-sensing receptor in the gastrointestinal tract. Cell Calcium 2004, 35: 239-247. PMID: 15200147, DOI: 10.1016/j.ceca.2003.10.015.Peer-Reviewed Original ResearchConceptsNormal cell proliferationGastrointestinal tractEpithelial cellsNutrient availabilityIntestinal epithelial cellsPotential roleGastrointestinal epithelial cellsL-amino acidsFood digestionRapid turnoverNutrient absorptionCell proliferationWater homeostasisGastric acid secretionGastrointestinal biologyEntire gastrointestinal tractAllosteric modifierCalcium intakeSecretory diarrheaAcid secretionCalcium handlingExtracellular Ca2Colon cancerReceptorsPhysiological effectsExtracellular polyamines regulate fluid secretion in rat colonic crypts via the extracellular calcium-sensing receptor
Cheng SX, Geibel JP, Hebert SC. Extracellular polyamines regulate fluid secretion in rat colonic crypts via the extracellular calcium-sensing receptor. Gastroenterology 2004, 126: 148-158. PMID: 14699496, DOI: 10.1053/j.gastro.2003.10.064.Peer-Reviewed Original ResearchConceptsCalcium-sensing receptorColonic epithelial cellsFluid secretionColonic cryptsCalcium-sensing receptor activationExtracellular calcium-sensing receptorEpithelial cellsIntracellular D-myo-inositolNormal postnatal developmentRat colonic cryptsExtracellular polyaminesDistal colonDistal colonic cryptsSecond messenger generationDistal colonic epithelial cellsGastrointestinal epitheliumSecond messenger accumulationPostnatal developmentReceptor activationExtracellular spermineIntact cryptsReceptorsColonocyte functionSecretionCrypts
2002
Expression of calcium-sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion
Cheng SX, Okuda M, Hall AE, Geibel JP, Hebert SC. Expression of calcium-sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion. AJP Gastrointestinal And Liver Physiology 2002, 283: g240-g250. PMID: 12065312, DOI: 10.1152/ajpgi.00500.2001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportBody FluidsCalciumCell LineCell MembraneColonHumansIn Vitro TechniquesIntestinal MucosaIntracellular MembranesMalePhosphatidylinositol Diacylglycerol-LyaseRatsRats, Sprague-DawleyReceptors, Calcium-SensingReceptors, Cell SurfaceTranscription, GeneticType C PhospholipasesConceptsCalcium-sensing receptorCrypt cellsFluid secretionNet fluid secretionIntestinal fluid transportRat colonic epitheliumCaSR agonistsIntracellular calciumExtracellular calciumColonic epitheliumDiarrheal diseaseCaSR transcriptsBath perfusateStimulatory effectBody cellsSecretionReceptorsCryptsElevated cAMPBasolateral surfaceCellsDivalent mineralsCalciumCaSRAgonists