Metformin Transport in Native MDCK-Wt and MDCK-II Monolayers Unveils Functional Inter-Strains Differences Influencing Drug Permeability

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dc.catalogadorvzp
dc.contributor.authorGarcía Alcalde, Mauricio Andrés
dc.contributor.authorContreras Valverde, Danae Valentina
dc.contributor.authorGonzalez, Pablo M.
dc.date.accessioned2024-12-31T13:46:15Z
dc.date.available2024-12-31T13:46:15Z
dc.date.issued2020
dc.description.abstractPurposeMDCK cells are commonly used to assess drug permeability, but the existence of various strains merits a comparative functional study. Since metformin absorption is largely mediated by transporters and paracellular diffusion, we used it to functionally compare MDCK-wt and MDCK-II.MethodsUptake, bidirectional transport and efflux experiments were performed using different buffers, pH, and a panel of transporter inhibitors. Relative contributions to total transport in both strains were estimated.ResultsMetformin uptake into MDCK-wt was linear but saturable in MDCK-II. Uptake into MDCK-wt or -II was promoted at pH 5.4 or 8.4, respectively. Quinidine and cimetidine similarly inhibited uptake in both strains. Lopinavir (PMAT specific) at pH 5.4 or pyrimethamine (MATE specific) at pH 8.4 differentially inhibited MDCK-wt or -II, respectively. Transport at pH 7.4 was absorptive regardless of strains, but secretory (MDCK-II) or absorptive (MDCK-wt) at pH 5.4. Efflux was largely basolateral in both strains. While paracellular permeability was similar between strains, total transport was dominated by transporters in MDCK-II or paracellular diffusion in MDCK-wt.ConclusionsMetformin transport revealed functional differences between MDCK strains. Apical uptake was governed by MATE in MDCK-II or PMAT in MDCK-wt, such that metformin transport was either secretory or absorptive, respectively.
dc.description.funderFondo Nacional de Desarrollo Cientifico Tecnologico de Chile (FONDECYT)
dc.description.funderFondo para Equipamiento Cientifico y Tecnologico (FONDEQUIP)
dc.description.funderFondo de Fomento al Desarrollo Cientifico y Tecnologico (FONDEF)
dc.format.extent14 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1007/s11095-020-02824-w
dc.identifier.eissn1573-904X
dc.identifier.issn0724-8741
dc.identifier.pubmedidMEDLINE:32514792
dc.identifier.urihttps://doi.org/10.1007/s11095-020-02824-w
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/89413
dc.identifier.wosidWOS:000541067500002
dc.information.autorucEscuela de Química; García Alcalde, Mauricio Andrés; S/I; 181066
dc.information.autorucEscuela de Química; Contreras Valverde, Danae Valentina; S/I; 223515
dc.issue.numero121
dc.language.isoen
dc.nota.accesocontenido parcial
dc.publisherSPRINGER/PLENUM PUBLISHERS
dc.revistaPharmaceutical Research
dc.rightsacceso restringido
dc.subjectMDCK cells
dc.subjectMetformin
dc.subjectPermeability
dc.subjectParacellular
dc.subjectTransporters
dc.subjectORGANIC CATION TRANSPORTER
dc.subjectEPITHELIAL-CELLS
dc.subjectMULTIDRUG
dc.subjectPROTEIN
dc.subjectMODEL
dc.subjectIDENTIFICATION
dc.subjectCHOLINE
dc.subjectCACO-2
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleMetformin Transport in Native MDCK-Wt and MDCK-II Monolayers Unveils Functional Inter-Strains Differences Influencing Drug Permeability
dc.typeartículo
dc.volumen37
sipa.codpersvinculados181066
sipa.codpersvinculados223515
sipa.trazabilidadWOS;05-06-2021
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