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 modelNeratinibActivation of the Calcium Sensing Receptor Decreases Secretagogue-Induced Fluid Secretion in the Rat Small Intestine
Barahona MJ, Maina RM, Lysyy T, Finotti M, Caturegli G, Baratta V, D’Amico F, Mulligan D, Geibel JP. Activation of the Calcium Sensing Receptor Decreases Secretagogue-Induced Fluid Secretion in the Rat Small Intestine. Frontiers In Physiology 2019, 10: 439. PMID: 31130866, PMCID: PMC6509940, DOI: 10.3389/fphys.2019.00439.Peer-Reviewed Original ResearchPresence of forskolinFluid secretionSmall intestineAC-265347Fluid absorptionIntestinal fluid secretionCalcium-sensing receptorSprague-Dawley ratsNew therapeutic targetsNet fluid absorptionDose-dependent mannerRat small intestineMM CaAbsence of forskolinMammalian gastrointestinal tractFluid hypersecretionDiarrheal illnessIntraluminal perfusionPotent secretagogueDawley ratsGastrointestinal tractCaSR activatorsElectrolyte balanceTherapeutic targetLuminal perfusateDesign 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 ResearchConceptsSignificant 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
Activation of the Calcium Sensing Receptor (casr) Prevents Secretagogue-Induced Diarrhea in the Rat Small Intestine
Finotti M, Lysyy T, Caturegli G, Barahona M, Maina R, D'Amico F, Mulligan D, Geibel J. Activation of the Calcium Sensing Receptor (casr) Prevents Secretagogue-Induced Diarrhea in the Rat Small Intestine. Transplantation 2018, 102: s669. DOI: 10.1097/01.tp.0000543607.00911.f4.Peer-Reviewed Original ResearchOral rehydration solutionSmall intestineColon segmentsIntestinal secretionNumerous body tissuesSeverity of diarrheaDistal small intestineMale Sprague-DawleyCalcium-sensing receptorDistal portionLuminal calcium concentrationRat small intestineAbsence of forskolinCalcium perfusionProphylactic therapyAntibiotic therapyLeading causePotent secretagogueRehydration solutionSprague-DawleyElectrolyte homeostasisDiarrheaPotential treatmentSecretion profileAbsorption of fluid
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 ResearchConceptsBone metabolismGastric acid secretionCalcium-sensing receptorVitamin DParathyroid glandsAcid secretionGastrointestinal organsTherapeutic implicationsEndocrine modulatorsCalcium homeostasisDiseaseStomachOrgansMetabolismImportant playersIntermediary organDiverse tissuesDysfunctionCaSRPTHCalcitoninKidneySecretionIntestineReceptorsChapter 2 Molecular Aspects of the Calcium-Sensing Receptor and Calcium Homeostasis
Alkukhun A, Munoz-Abraham A, Judeeba S, Geibel J. Chapter 2 Molecular Aspects of the Calcium-Sensing Receptor and Calcium Homeostasis. 2017, 15-26. DOI: 10.1016/b978-0-12-802168-2.00002-6.ChaptersCalcium homeostasisImmune barrier functionCalcium sensing receptorGastric acid secretionCalcium-sensing receptorExtracellular calcium levelsVitamin DAntidiarrheal effectBile flowHormone secretionParathyroid glandsImmune responseGastrointestinal tractAcid secretionIntestinal floraElectrolyte balanceCalcium levelsBone mineralizationBarrier functionCaSROsteoclast proliferationKey modulatorReceptorsSecretionPhysiological functions
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
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 membraneChapter 63 The Calcium-Sensing Receptor
Brown E, Hebert S, Riccardi D, Geibel J. Chapter 63 The Calcium-Sensing Receptor. 2013, 2187-2224. DOI: 10.1016/b978-0-12-381462-3.00063-x.Peer-Reviewed Original ResearchIon homeostasisMineral ion homeostasisCell surface sensorsDiverse physiological processesG protein-coupled receptorsCalcium sensing receptorPrimary physiological ligandProtein-coupled receptorsCellular processesExtracellular calcium-sensing receptorAromatic amino acidsAquatic animalsBiological roleWhole organismPhysiological processesFirst messengersPhysiological ligandsPhospholipase CAmino acidsCalcium-sensing receptorHomeostatic processesCalciostatHomeostasisAutosomal dominant hypocalcemiaExtracellular Ca2
2010
The calcium-sensing receptor.
Geibel JP. The calcium-sensing receptor. Journal Of Nephrology 2010, 23 Suppl 16: s130-5. PMID: 21170870.Peer-Reviewed Original ResearchConceptsCalcium-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 ResearchConceptsGastrointestinal 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
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 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
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
Extracellular 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
2001
The 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