HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yamashita, T. Articles by Tohyama, M. Search for Related Content PubMed PubMed Citation Articles by Yamashita, T. Articles by Tohyama, M. Social Bookmarking                      What's this?

Volume 272, Number 15, Issue of April 11, 1997 pp. 10205-10211
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Cloning and Functional Expression of a Brain Peptide/Histidine Transporter

(Received for publication, October 31, 1996, and in revised form, January 15, 1997)

Toshihide Yamashita ^§¶ , Shoichi Shimada ^§ , Wei Guo ^§ , Kohji Sato ^§ , Eiji Kohmura ^¶ , Toru Hayakawa ^¶ , Tsutomu Takagi and Masaya Tohyama ^§

From the Departments of  Molecular Neurobiology (TANABE), ^§ Anatomy and Neuroscience, and ^¶ Neurosurgery, Osaka University School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565, Japan

Here we report the cloning and functional characterization of a rat novel peptide/histidine transporter (PHT1), which was expressed in the brain and the retina. The cDNA encodes the predicted protein of 572 amino acid residues with 12 putative membrane-spanning domains. The amino acid sequence has moderate homology with a nonspecific peptide transporter found in the plant. When expressed in Xenopus laevis oocytes, PHT1 cRNA induced high affinity proton-dependent histidine transport activity. This transport process was inhibited by dipeptides and tripeptides but not by free amino acids such as glutamate, glycine, leucine, methionine, and aspartate. Dipeptide carnosine transport activity was also confirmed by direct uptake measurement. By in situ hybridization analysis, PHT1 mRNA was widely distributed throughout whole brain. Especially, intense hybridization signals were found in the hippocampus, choroid plexus, cerebellum, and pontine nucleus. Signals were located in both the neuronal and small nonneuronal cells in these areas. PHT1 protein could contribute to uptake of oligopeptides, which function as neuromodulators, and clearance of degraded neuropeptides and be a new member in the growing superfamily of proton-coupled peptide and nitrate transporters, although its structure, localization, and pharmacological characteristics are unique among these members.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S.-H. Lin, H.-F. Kuo, G. Canivenc, C.-S. Lin, M. Lepetit, P.-K. Hsu, P. Tillard, H.-L. Lin, Y.-Y. Wang, C.-B. Tsai, et al. Mutation of the Arabidopsis NRT1.5 Nitrate Transporter Causes Defective Root-to-Shoot Nitrate Transport PLANT CELL, September 1, 2008; 20(9): 2514 - 2528. [Abstract] [Full Text] [PDF]

				I. M. Frey, I. Rubio-Aliaga, A. Siewert, D. Sailer, A. Drobyshev, J. Beckers, M. H. de Angelis, J. Aubert, A. B. Hen, O. Fiehn, et al. Profiling at mRNA, protein, and metabolite levels reveals alterations in renal amino acid handling and glutathione metabolism in kidney tissue of Pept2-/- mice Physiol Genomics, February 12, 2007; 28(3): 301 - 310. [Abstract] [Full Text] [PDF]

				H. Daniel, B. Spanier, G. Kottra, and D. Weitz From Bacteria to Man: Archaic Proton-Dependent Peptide Transporters at Work Physiology, April 1, 2006; 21(2): 93 - 102. [Abstract] [Full Text] [PDF]

				X. Cen, A. Nitta, S. Ohya, Y. Zhao, N. Ozawa, A. Mouri, D. Ibi, L. Wang, M. Suzuki, K. Saito, et al. An analog of a dipeptide-like structure of FK506 increases glial cell line-derived neurotrophic factor expression through cAMP response element-binding protein activated by heat shock protein 90/Akt signaling pathway. J. Neurosci., March 22, 2006; 26(12): 3335 - 3344. [Abstract] [Full Text] [PDF]

				H. Shen, R. F. Keep, Y. Hu, and D. E. Smith PEPT2 (Slc15a2)-Mediated Unidirectional Transport of Cefadroxil from Cerebrospinal Fluid into Choroid Plexus J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1101 - 1108. [Abstract] [Full Text] [PDF]

				S. M. Ocheltree, H. Shen, Y. Hu, R. F. Keep, and D. E. Smith Role and Relevance of Peptide Transporter 2 (PEPT2) in the Kidney and Choroid Plexus: In Vivo Studies with Glycylsarcosine in Wild-Type and PEPT2 Knockout Mice J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 240 - 247. [Abstract] [Full Text] [PDF]

				B. S. Anand, S. Katragadda, and A. K. Mitra Pharmacokinetics of Novel Dipeptide Ester Prodrugs of Acyclovir after Oral Administration: Intestinal Absorption and Liver Metabolism J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 659 - 667. [Abstract] [Full Text] [PDF]

				C.-S. Chiang, G. Stacey, and Y.-F. Tsay Mechanisms and Functional Properties of Two Peptide Transporters, AtPTR2 and fPTR2 J. Biol. Chem., July 16, 2004; 279(29): 30150 - 30157. [Abstract] [Full Text] [PDF]

				S. M. Ocheltree, H. Shen, Y. Hu, J. Xiang, R. F. Keep, and D. E. Smith Mechanisms of Cefadroxil Uptake in the Choroid Plexus: Studies in Wild-Type and PEPT2 Knockout Mice J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 462 - 467. [Abstract] [Full Text] [PDF]

				I. Rubio-Aliaga, I. Frey, M. Boll, D. A. Groneberg, H. M. Eichinger, R. Balling, and H. Daniel Targeted Disruption of the Peptide Transporter Pept2 Gene in Mice Defines Its Physiological Role in the Kidney Mol. Cell. Biol., May 1, 2003; 23(9): 3247 - 3252. [Abstract] [Full Text] [PDF]

				H. Daniel and I. Rubio-Aliaga An update on renal peptide transporters Am J Physiol Renal Physiol, May 1, 2003; 284(5): F885 - F892. [Abstract] [Full Text] [PDF]

				H. Toyobuku, Y. Sai, T. Kagami, I. Tamai, and A. Tsuji Delivery of Peptide Drugs to the Brain by Adenovirus-Mediated Heterologous Expression of Human Oligopeptide Transporter at the Blood-Brain Barrier J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 40 - 47. [Abstract] [Full Text]

				H. Shen, D. E. Smith, R. F. Keep, J. Xiang, and F. C. Brosius III Targeted Disruption of the PEPT2 Gene Markedly Reduces Dipeptide Uptake in Choroid Plexus J. Biol. Chem., February 7, 2003; 278(7): 4786 - 4791. [Abstract] [Full Text] [PDF]

				C. Shu, H. Shen, N. S. Teuscher, P. J. Lorenzi, R. F. Keep, and D. E. Smith 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., June 1, 2002; 301(3): 820 - 829. [Abstract] [Full Text] [PDF]

				S. Ugawa, Y. Sunouchi, T. Ueda, E. Takahashi, Y. Saishin, and S. Shimada Characterization of a mouse colonic system B0+ amino acid transporter related to amino acid absorption in colon Am J Physiol Gastrointest Liver Physiol, August 1, 2001; 281(2): G365 - G370. [Abstract] [Full Text] [PDF]

				Y.-H. Han, D. H. Sweet, D.-N. Hu, and J. B. Pritchard Characterization of a Novel Cationic Drug Transporter in Human Retinal Pigment Epithelial Cells J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 450 - 457. [Abstract] [Full Text]

				N. S. Teuscher, A. Novotny, R. F. Keep, and D. E. Smith Functional Evidence for Presence of PEPT2 in Rat Choroid Plexus: Studies with Glycylsarcosine J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 494 - 499. [Abstract] [Full Text]

				Y. Saishin, R. Ishikawa, S. Ugawa, W. Guo, T. Ueda, H. Morimura, K. Kohama, H. Shimizu, Y. Tano, and S. Shimada Retinal Fascin: Functional Nature, Subcellular Distribution, and Chromosomal Localization Invest. Ophthalmol. Vis. Sci., July 1, 2000; 41(8): 2087 - 2095. [Abstract] [Full Text]

				C.-M. Lin, S. Koh, G. Stacey, S.-M. Yu, T.-Y. Lin, and Y.-F. Tsay Cloning and Functional Characterization of a Constitutively Expressed Nitrate Transporter Gene, OsNRT1, from Rice Plant Physiology, February 1, 2000; 122(2): 379 - 388. [Abstract] [Full Text]

				N.-C. Huang, K.-H. Liu, H.-J. Lo, and Y.-F. Tsay Cloning and Functional Characterization of an Arabidopsis Nitrate Transporter Gene That Encodes a Constitutive Component of Low-Affinity Uptake PLANT CELL, August 1, 1999; 11(8): 1381 - 1392. [Abstract] [Full Text]

				H. Wang, Y.-J. Fei, V. Ganapathy, and F. H. Leibach Electrophysiological characteristics of the proton-coupled peptide transporter PEPT2 cloned from rat brain Am J Physiol Cell Physiol, October 1, 1998; 275(4): C967 - C975. [Abstract] [Full Text] [PDF]

				J.-J. Zhou, F. L. Theodoulou, I. Muldin, B. Ingemarsson, and A. J. Miller Cloning and Functional Characterization of a Brassica napus Transporter That Is Able to Transport Nitrate and Histidine J. Biol. Chem., May 15, 1998; 273(20): 12017 - 12023. [Abstract] [Full Text] [PDF]