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Divergent developmental expression and function of the proton‐coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and rat

dc.contributor.authorHu, Yongjunen_US
dc.contributor.authorXie, Yehuaen_US
dc.contributor.authorKeep, Richard F.en_US
dc.contributor.authorSmith, David E.en_US
dc.date.accessioned2014-07-03T14:41:17Z
dc.date.availableWITHHELD_12_MONTHSen_US
dc.date.available2014-07-03T14:41:17Z
dc.date.issued2014-06en_US
dc.identifier.citationHu, Yongjun; Xie, Yehua; Keep, Richard F.; Smith, David E. (2014). "Divergent developmental expression and function of the proton‐coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and rat." Journal of Neurochemistry 129(6): 955-965.en_US
dc.identifier.issn0022-3042en_US
dc.identifier.issn1471-4159en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/107491
dc.description.abstractThis study evaluated the developmental gene and protein expression of proton‐coupled oligopeptide transporters ( POT s: peptide transporter, PepT1 and PepT2; peptide‐histidine transporter, PhT1 and PhT2) in different regions of rodent brain, and the age‐dependent uptake of a POT substrate, glycylsarcosine (GlySar), in brain slices. Slices were obtained from cerebral cortex, cerebellum and hippocampus of wildtype and PepT2 null mice, and from rats at different ages. Gene and protein expression were determined by real‐time PCR and immunoblot analyses. Brain slice uptakes of radiolabeled glycylsarcosine were determined in the absence and presence of excess unlabeled glycylsarcosine or l ‐histidine, the latter being an inhibitor of PhT1/2 but not PepT1/2. As PepT2 and PhT1 transcripts were abundantly expressed in all three regions of mouse brain, little to no expression was observed for PepT1 and PhT2. PhT1 protein was present in brain regions of adult but not neonatal mice and expression levels increased with age in rats. Glycylsarcosine uptake, inhibition and transporter dominance did not show regional brain or species differences. However, there were clear age‐related differences in functional activity, with PepT2 dominating in neonatal mice and rats, and PhT1 dominating in adult rodents. These developmental changes may markedly impact the neural activity of both endogenous and exogenous (drug) peptides/mimetics. Developmental gene and protein expression of peptide transporters was evaluated in various regions of rodent brain, along with age‐dependent uptake of dipeptide. We found marked changes in protein expression and functional activity of PhT1 and PepT2, the former predominating in adult and the latter in neonate. These developmental changes may markedly impact the neural activity of endogenous and exogenous peptides/mimetics. Developmental gene and protein expression of peptide transporters was evaluated in various regions of rodent brain, along with age‐dependent uptake of dipeptide. We found marked changes in protein expression and functional activity of PhT1 and PepT2, the former predominating in adult and the latter in neonate. These developmental changes may markedly impact the neural activity of endogenous and exogenous peptides/mimetics.en_US
dc.publisherWiley Periodicals, Inc.en_US
dc.publisherElsevieren_US
dc.subject.otherExpressionen_US
dc.subject.otherFunctionen_US
dc.subject.otherPepT2en_US
dc.subject.otherBrainen_US
dc.subject.otherDevelopmenten_US
dc.subject.otherPhT1en_US
dc.titleDivergent developmental expression and function of the proton‐coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and raten_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelNeurosciencesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/107491/1/jnc12687.pdf
dc.identifier.doi10.1111/jnc.12687en_US
dc.identifier.sourceJournal of Neurochemistryen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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