Divergent developmental expression and function of the proton‐coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and rat
dc.contributor.author | Hu, Yongjun | en_US |
dc.contributor.author | Xie, Yehua | en_US |
dc.contributor.author | Keep, Richard F. | en_US |
dc.contributor.author | Smith, David E. | en_US |
dc.date.accessioned | 2014-07-03T14:41:17Z | |
dc.date.available | WITHHELD_12_MONTHS | en_US |
dc.date.available | 2014-07-03T14:41:17Z | |
dc.date.issued | 2014-06 | en_US |
dc.identifier.citation | Hu, 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.issn | 0022-3042 | en_US |
dc.identifier.issn | 1471-4159 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/107491 | |
dc.description.abstract | This 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.publisher | Wiley Periodicals, Inc. | en_US |
dc.publisher | Elsevier | en_US |
dc.subject.other | Expression | en_US |
dc.subject.other | Function | en_US |
dc.subject.other | PepT2 | en_US |
dc.subject.other | Brain | en_US |
dc.subject.other | Development | en_US |
dc.subject.other | PhT1 | en_US |
dc.title | Divergent developmental expression and function of the proton‐coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and rat | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Neurosciences | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/107491/1/jnc12687.pdf | |
dc.identifier.doi | 10.1111/jnc.12687 | en_US |
dc.identifier.source | Journal of Neurochemistry | en_US |
dc.identifier.citedreference | Shen H., Smith D. E., Keep R. F., Xiang J. and Brosius F. C., 3rd ( 2003 ) Targeted disruption of the PEPT2 gene markedly reduces dipeptide uptake in choroid plexus. J. Biol. Chem. 278, 4786 – 4791. | en_US |
dc.identifier.citedreference | Lee H. S., Kim T., Bang S. Y. et al. ( 2013 ) Ethnic specificity of lupus‐associated loci identified in a genome‐wide association study in Korean women. Ann. Rheum. Dis., doi: 10.1136/annrheumdis‐2012‐202675. [Epub ahead of print]. | en_US |
dc.identifier.citedreference | Martres M. P., Baudry M. and Schwartz J. C. ( 1975 ) Histamine synthesis in the developing rat brain: evidence for a multiple compartmentation. Brain Res. 83, 261 – 275. | en_US |
dc.identifier.citedreference | Nolan T., Hands R. E. and Bustin S. A. ( 2006 ) Quantification of mRNA using real‐time RT‐PCR. Nat. Protoc. 1, 1559 – 1582. | en_US |
dc.identifier.citedreference | Novotny A., Xiang J., Stummer W., Teuscher N. S., Smith D. E. and Keep R. F. ( 2000 ) Mechanisms of 5‐aminolevulinic acid uptake at the choroid plexus. J. Neurochem. 75, 321 – 328. | en_US |
dc.identifier.citedreference | Reid K. H., Edmonds H. L., Jr, Schurr A., Tseng M. T. and West C. A. ( 1988 ) Pitfalls in the use of brain slices. Prog. Neurobiol. 31, 1 – 18. | en_US |
dc.identifier.citedreference | Reiner P. B., Semba K., Fibiger H. C. and McGeer E. G. ( 1988 ) Ontogeny of histidine‐decarboxylase‐immunoreactive neurons in the tuberomammillary nucleus of the rat hypothalamus: time of origin and development of transmitter phenotype. J. Comp. Neurol. 276, 304 – 311. | en_US |
dc.identifier.citedreference | Rubio‐Aliaga I. and Daniel H. ( 2008 ) Peptide transporters and their roles in physiological processes and drug disposition. Xenobiotica 38, 1022 – 1042. | en_US |
dc.identifier.citedreference | Sakata K., Yamashita T., Maeda M., Moriyama Y., Shimada S. and Tohyama M. ( 2001 ) Cloning of a lymphatic peptide/histidine transporter. Biochem. J. 356, 53 – 60. | en_US |
dc.identifier.citedreference | Sasawatari S., Okamura T., Kasumi E., Tanaka‐Furuyama K., Yanobu‐Takanashi R., Shirasawa S., Kato N. and Toyama‐Sorimachi N. ( 2011 ) The solute carrier family 15A4 regulates TLR9 and NOD1 functions in the innate immune system and promotes colitis in mice. Gastroenterology 140, 1513 – 1525. | en_US |
dc.identifier.citedreference | Shen H., Smith D. E., Yang T., Huang Y. G., Schnermann J. B. and Brosius F. C., 3rd ( 1999 ) Localization of PEPT1 and PEPT2 proton‐coupled oligopeptide transporter mRNA and protein in rat kidney. Am. J. Physiol. 276, F658 – F665. | en_US |
dc.identifier.citedreference | Shen H., Smith D. E., Keep R. F. and Brosius F. C., 3rd ( 2004 ) Immunolocalization of the proton‐coupled oligopeptide transporter PEPT2 in developing rat brain. Mol. Pharm. 1, 248 – 256. | en_US |
dc.identifier.citedreference | Shu C., Shen H., Teuscher N. S., Lorenzi P. J., Keep R. F. and Smith D. E. ( 2002 ) Role of PEPT2 in peptide/mimetic trafficking at the blood‐cerebrospinal fluid barrier: studies in rat choroid plexus epithelial cells in primary culture. J. Pharmacol. Exp. Ther. 301, 820 – 829. | en_US |
dc.identifier.citedreference | Smith D. E., Johanson C. E. and Keep R. F. ( 2004 ) Peptide and peptide analog transport systems at the blood‐CSF barrier. Adv. Drug Deliv. Rev. 56, 1765 – 1791. | en_US |
dc.identifier.citedreference | Smith D. E., Hu Y., Shen H., Nagaraja T. N., Fenstermacher J. D. and Keep R. F. ( 2011 ) Distribution of glycylsarcosine and cefadroxil among cerebrospinal fluid, choroid plexus, and brain parenchyma after intracerebroventricular injection is markedly different between wild‐type and Pept2 null mice. J. Cereb. Blood Flow Metab. 31, 250 – 261. | en_US |
dc.identifier.citedreference | Smith D. E., Clémençon B. and Hediger M. A. ( 2013 ) Proton‐coupled oligopeptide transporter family SLC15: physiological, pharmacological and pathological implications. Mol. Aspects Med. 34, 323 – 336. | en_US |
dc.identifier.citedreference | Subramanian N., Whitmore W. L., Seidler F. J. and Slotkin T. A. ( 1981 ) Ontogeny of histaminergic neurotransmission in the rat brain: concomitant development of neuronal histamine, H‐1 receptors, and H‐1 receptor‐mediated stimulation of phospholipid turnover. J. Neurochem. 36, 1137 – 1141. | en_US |
dc.identifier.citedreference | Sun D., Wang Y., Tan F., Fang D., Hu Y., Smith D. E. and Jiang H. ( 2013 ) Functional and molecular expression of the proton‐coupled oligopeptide transporters in spleen and macrophages from mouse and human. Mol. Pharm. 10, 1409 – 1416. | en_US |
dc.identifier.citedreference | Teuscher N. S., Novotny A., Keep R. F. and Smith D. E. ( 2000 ) Functional evidence for presence of PEPT2 in rat choroid plexus: studies with glycylsarcosine. J. Pharmacol. Exp. Ther. 294, 494 – 499. | en_US |
dc.identifier.citedreference | Teuscher N. S., Keep R. F. and Smith D. E. ( 2001 ) PEPT2‐mediated uptake of neuropeptides in rat choroid plexus. Pharm. Res. 18, 807 – 813. | en_US |
dc.identifier.citedreference | Toledo A., Sabria J., Rodriguez R., Brandner R., Rodriguez J., Palacios J. M. and Blanco I. ( 1988 ) Properties and ontogenic development of membrane‐bound histidine decarboxylase from rat brain. J. Neurochem. 51, 1400 – 1406. | en_US |
dc.identifier.citedreference | Tran V. T., Freeman A. D., Chang R. S. and Snyder S. H. ( 1980 ) Ontogenetic development of histamine h1‐receptor binding in rat brain. J. Neurochem. 34, 1609 – 1613. | en_US |
dc.identifier.citedreference | Walker D., Thwaites D. T., Simmons N. L., Gilbert H. J. and Hirst B. H. ( 1998 ) Substrate upregulation of the human small intestinal peptide transporter, hPepT1. J. Physiol. 507, 697 – 706. | en_US |
dc.identifier.citedreference | Wang M., Zhang X., Zhao H., Wang Q. and Pan Y. ( 2010 ) Comparative analysis of vertebrate PEPT1 and PEPT2 genes. Genetica 138, 587 – 599. | en_US |
dc.identifier.citedreference | Yamashita T., Shimada S., Guo W., Sato K., Kohmura E., Hayakawa T., Takagi T. and Tohyama M. ( 1997 ) Cloning and functional expression of a brain peptide/histidine transporter. J. Biol. Chem. 272, 10205 – 10211. | en_US |
dc.identifier.citedreference | Baccala R., Gonzalez‐Quintial R., Blasius A. L., Rimann I., Ozato K., Kono D. H., Beutler B. and Theofilopoulos A. N. ( 2013 ) Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid dendritic cells in the pathogenesis of lupus. Proc. Natl Acad. Sci. USA 110, 2940 – 2945. | en_US |
dc.identifier.citedreference | Brandsch M., Knutter I. and Bosse‐Doenecke E. ( 2008 ) Pharmaceutical and pharmacological importance of peptide transporters. J. Pharm. Pharmacol. 60, 543 – 585. | en_US |
dc.identifier.citedreference | Daniel H. and Kottra G. ( 2004 ) The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology. Pflugers Arch. 447, 610 – 618. | en_US |
dc.identifier.citedreference | Dieck S. T., Heuer H., Ehrchen J., Otto C. and Bauer K. ( 1999 ) The peptide transporter PepT2 is expressed in rat brain and mediates the accumulation of the fluorescent dipeptide derivative β‐Ala‐Lys‐N ε ‐AMCA in astrocytes. Glia 25, 10 – 20. | en_US |
dc.identifier.citedreference | Dringen R., Hamprecht B. and Bröer S. ( 1998 ) The peptide transporter PepT2 mediates the uptake of the glutathione precursor CysGly in astroglia‐rich primary cultures. J. Neurochem. 71, 388 – 393. | en_US |
dc.identifier.citedreference | Fujita T., Kishida T., Okada N., Ganapathy V., Leibach F. H. and Yamamoto A. ( 1999 ) Interaction of kyotorphin and brain peptide transporter in synaptosomes prepared from rat cerebellum: Implication of high affinity type H + /peptide transporter PEPT2 mediated transport system. Neurosci. Lett. 271, 117 – 120. | en_US |
dc.identifier.citedreference | Fujita T., Kishida T., Wada M., Okada N., Yamamoto A., Leibach F. H. and Ganapathy V. ( 2004 ) Functional characterization of brain peptide transporter in rat cerebral cortex: identification of the high‐affinity type H + /peptide transporter PEPT2. Brain Res. 997, 52 – 61. | en_US |
dc.identifier.citedreference | Groneberg D. A., Doring F., Eynott P. R., Fischer A. and Daniel H. ( 2001 ) Intestinal peptide transport: ex vivo uptake studies and localization of peptide carrier PEPT1. Am. J. Physiol. Gastrointest. Liver Physiol. 281, G697 – G704. | en_US |
dc.identifier.citedreference | Haas H. L., Sergeeva O. A. and Selbach O. ( 2008 ) Histamine in the nervous system. Physiol. Rev. 88, 1183 – 1241. | en_US |
dc.identifier.citedreference | Han J.‐W., Zheng H.‐F., Cui Y. et al. ( 2009 ) Genome‐wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat. Genet. 41, 1234 – 1237. | en_US |
dc.identifier.citedreference | He C. F., Liu Y. S., Cheng Y. L. et al. ( 2010 ) TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1 are associated with clinical features of systemic lupus erythematosus in a Chinese Han population. Lupus 19, 1181 – 1186. | en_US |
dc.identifier.citedreference | Herrera‐Ruiz D. and Knipp G. T. ( 2003 ) Current perspectives on established and putative mammalian oligopeptide transporters. J. Pharm. Sci. 92, 691 – 714. | en_US |
dc.identifier.citedreference | Hough L. B. and Leurs R. ( 2006 ) Histamine, in Basic Neurochemistry: Molecular, Cellular, and Medical Aspects ( Siegel G. J., Albers R. W., Brady S. T. and Price D. L., eds), 7th edn, pp. 249 – 265. Elsevier, London. | en_US |
dc.identifier.citedreference | Hu Y., Shen H., Keep R. F. and Smith D. E. ( 2007 ) Peptide transporter 2 (PEPT2) expression in brain protects against 5‐aminolevulinic acid neurotoxicity. J. Neurochem. 103, 2058 – 2065. | en_US |
dc.identifier.citedreference | Jappar D., Wu S. P., Hu Y. and Smith D. E. ( 2010 ) Significance and regional dependency of peptide transporter (PEPT) 1 in the intestinal permeability of glycylsarcosine: in situ single‐pass perfusion studies in wild‐type and Pept1 knockout mice. Drug Metab. Dispos. 38, 1740 – 1746. | en_US |
dc.identifier.citedreference | Jiang H., Hu Y., Keep R. F. and Smith D. E. ( 2009 ) Enhanced antinociceptive response to intracerebroventricular kyotorphin in Pept2 null mice. J. Neurochem. 109, 1536 – 1543. | en_US |
dc.identifier.citedreference | Kamal M. A., Keep R. F. and Smith D. E. ( 2008 ) Role and relevance of PEPT2 in drug disposition, dynamics, and toxicity. Drug Metab. Pharmacokinet. 23, 236 – 242. | en_US |
dc.identifier.citedreference | Keep R. F. and Smith D. E. ( 2013 ) Oligopeptide and peptide‐like drug transport, in The Handbook of Biologically Active Peptides, ( Kastin A. J., ed.), pp. 1688 – 1695. Elsevier, Burlington. | en_US |
dc.identifier.citedreference | Lee J., Tattoli I., Wojtal K. A., Vavricka S. R., Philpott D. J. and Girardin S. E. ( 2009 ) pH‐dependent internalization of muramyl peptides from early endosomes enables Nod1 and Nod2 signaling. J. Biol. Chem. 284, 23818 – 23829. | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.