Glutamate uptake system in the presynaptic vesicle: Glutamic acid analogs as inhibitors and alternate substrates
dc.contributor.author | Ueda, Tetsufumi | en_US |
dc.contributor.author | Winter, Harry C. | en_US |
dc.date.accessioned | 2006-09-11T16:01:22Z | |
dc.date.available | 2006-09-11T16:01:22Z | |
dc.date.issued | 1993-01 | en_US |
dc.identifier.citation | Winter, Harry C.; Ueda, Tetsufumi; (1993). "Glutamate uptake system in the presynaptic vesicle: Glutamic acid analogs as inhibitors and alternate substrates." Neurochemical Research 18(1): 79-85. <http://hdl.handle.net/2027.42/45406> | en_US |
dc.identifier.issn | 0364-3190 | en_US |
dc.identifier.issn | 1573-6903 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/45406 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=8096630&dopt=citation | en_US |
dc.description.abstract | A variety of naturally occurring amino acids, their isomers, and synthetic analogs were tested for their ability to inhibit uptake of [ 3 H]glutamate into presynaptic vesicles from bovine cerebral cortex. Strongest inhibition (K i <1mM) was observed for trans -1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) and erythro -4-methyl-L-glutamic acid (MGlu), while 4-methylene-L-glutamic acid (MeGlu) was only moderately inhibitory (Ki=∼3mM), indicating that the synaptic vesicle glutamate translocator has higher affinity for rans -ACPD and MGlu than for glutamate. A few other amino acids, e.g., 4-hydroxyglutamic acid, S-carboxyethyl cysteine, and 5-fluorotryptophan, were slightly inhibitory; all l - and dl -isomers of protein amino acids and longer chain acidic amino acids were without measurable inhibition. Potassium tetrathionate and S-sulfocysteine exhibited strong to moderate noncompetitive or irreversible inhibition. Inhibition by t-ACPD, MGlu, or MeGlu was competitive with glutamic acid. Each of these competitive inhibitors was also taken up by the vesicle preparation in an ATP-dependent manner, as indicated by their being recovered unchanged from filtered vesicles. Similar results were obtained with reconstituted vesicles, while glutamate uptake by partially purified rat synaptosomes was inhibited only by MGlu. These results indicate that the glutamate translocator of presynaptic vesicles has stringent structural requirements distinct from those of the plasma membrane translocator and the metabotropic type of postsynaptic glutamate receptor. They further suggest possible structural requirements of pharmacologically significant compounds that can substitute for glutamic acid in the presynaptic side of glutamatergic synapses, thus serving to moderate or control glutamate excitation and associated excitotoxic effects in these neurons. | en_US |
dc.format.extent | 696838 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Kluwer Academic Publishers-Plenum Publishers; Plenum Publishing Corporation ; Springer Science+Business Media | en_US |
dc.subject.other | Glutamate | en_US |
dc.subject.other | Biochemistry, General | en_US |
dc.subject.other | Neurosciences | en_US |
dc.subject.other | Biomedicine | en_US |
dc.subject.other | Neurology | en_US |
dc.subject.other | Synaptic Vesicles | en_US |
dc.subject.other | ACPD | en_US |
dc.subject.other | Neurotransmitters | en_US |
dc.title | Glutamate uptake system in the presynaptic vesicle: Glutamic acid analogs as inhibitors and alternate substrates | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbsecondlevel | Psychology | en_US |
dc.subject.hlbsecondlevel | Neurosciences | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Social Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Biological Chemistry, Medical School, and Mental Health Research Institute, The University of Michigan, 48109, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | Department of Pharmacology, Medical School, and Mental Health Research Institute, The University of Michigan, 48109, Ann Arbor, MI; Mental Health Research Institute, The University of Michigan, 205 Zina Pitcher Place, 48109-0720, Ann Arbor, MI | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 8096630 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/45406/1/11064_2004_Article_BF00966925.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1007/BF00966925 | en_US |
dc.identifier.source | Neurochemical Research | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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