Ken Curry - Academia.edu (original) (raw)

Papers by Ken Curry

Research paper thumbnail of Methionine sulfoximine shows excitotoxic actions in rat cortical slices

Canadian Journal of Physiology and Pharmacology, 1999

Methionine sulfoximine (MSO) is a rare amino acid. It occurs in nature or as a by-product of some... more Methionine sulfoximine (MSO) is a rare amino acid. It occurs in nature or as a by-product of some forms of food processing. A notable example of the latter was a former method for bleaching wheat flour, using nitrogen trichloride, the "agene process," in use for most of the first 50 years of this century. "Agenized" flour was found to be responsible for various neurological disorders in animals, and MSO was identified as the toxic factor. The agene process was subsequently discontinued in the United States and the United Kingdom circa 1950. MSO inhibits the synthesis of both glutathione and glutamine, and it is possible that its actions on the nervous system arise from alterations in the amount or distribution of these molecules. Structurally, MSO resembles glutamate, an observation that has also raised the possibility that it might have more direct glutamate-like actions on neurons. In the present investigation, we report excitatory and toxic actions of MSO in an in vitro preparation of adult rat cortex. Field potential recordings in this preparation show that MSO application evokes a sustained depolarization, which can be blocked by the N-methyl-D-aspartate (NMDA) antagonist L-(+)-2-amino-5-phosphonovalerate (AP5). However, competition assays using MSO on [3H]CGP-39653 (DL-(E)-2-amino-4-propyl-1-phosphono-3-pentenoate) binding in rat cortical homogenates show only 20% displacement of total binding, suggesting that MSO is acting indirectly, perhaps by releasing glutamate. To investigate this possibility, we measured glutamate release during MSO application. Time course and dose-response experiments with MSO showed significant [3H]glutamate release, which was partially attenuated by AP5. To assess cellular toxicity, we measured lactate dehydrogenase (LDH) release from cortical sections exposed to MSO. MSO treatment led to a rapid increase in LDH activity, which could be blocked by AP5. These data suggest that MSO acts by increasing glutamate release, which then activates NMDA receptors, leading to excitotoxic cell death. These data suggest the possibility that MSO in processed flour had excitotoxic actions that may have been contributing factors to some human neuronal disorders.Key words: agene process, glutamate release, lactate dehydrogenase, methionine sulfoximine, N-methyl-D-aspartate (NMDA) receptor, neurological disorders.

Research paper thumbnail of Characterization of a metabotropic glutamate receptor: direct negative coupling to adenylyl cyclase and involvement of a pertussis toxin-sensitive G protein

Proceedings of the National Academy of Sciences of the United States of America, Sep 1, 1992

Research paper thumbnail of Enantioselective synthesis of both enantiomers of the neuroexcitant 2-amino-3-(3-hydroxy-5- tert -butylisoxazol-4-yl) propanoic acid (ATPA)

Tetrahedron-asymmetry, Dec 1, 2000

Research paper thumbnail of Ca 2+ -dependent depolarization and burst firing of rat CA1 pyramidal neurones induced by N -methyl- D -aspartic acid and quinolinic acid: antagonism by 2-amino-5-phosphonovaleric and kynurenic acids

Canadian Journal of Physiology and Pharmacology, 1986

The excitatory effects of microiontophoretically applied quisqualic (QUIS), N-methyl-D-aspartic (... more The excitatory effects of microiontophoretically applied quisqualic (QUIS), N-methyl-D-aspartic (NMDA), and quinolinic (QUIN) acids were investigated using intracellular recording from CA1 pyramidal neurones in slices of rat hippocampus. QUIS evoked only simple action potentials superimposed upon a depolarization which attained a clear plateau. When this level had been reached, increased ejecting currents did not produce further depolarization. By contrast, with low currents NMD A and QUIN elicited small membrane depolarizations which triggered bursts of action potentials superimposed upon rhythmically occurring depolarizing shifts. Larger currents caused depolarization which if sufficiently large completely blocked spike activity. Tetrodotoxin (TTX) prevented the spikes evoked by QUIS and the bursts of action potentials seen with NMDA and QUIN, and the rhythmic depolarizing shifts then appeared as broad spikes of up to 50 mV in amplitude. These and the underlying membrane depolariz...

Research paper thumbnail of MOLECULAR PHARMACOLOGY, 42:322-327 Both Enantiomers of 1-Aminocyclopentyl-1,3-.dicarboxylate Are Full Agonists of Metabotropic Glutamate Receptors Coupled to

We tested the effects of two enantiomers of a glutamate ana-

Research paper thumbnail of Psychiatric Drug Discovery and Development--SRI's Third Annual Conference

Research paper thumbnail of Single channel properties of the N-methyl-D-aspartate receptor channel using NMDA and NMDA agonists: on-cell recordings

Experimental Brain Research

Research paper thumbnail of The actions of a conformationally restricted analogue of aspartic acid on mammalian spinal neurones

Neuroscience Letters

ABSTRACT

Research paper thumbnail of Synthesis, resolution, and absolute configuration of the isomers of the neuronal excitant 1-amino-1,3-cyclopentanedicarboxylic acid

Journal of Medicinal Chemistry

Research paper thumbnail of Psychiatric Drug Discovery and Development--SRI's Third Annual Conference

IDrugs : the investigational drugs journal, 2005

Research paper thumbnail of Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants: comparison with mGluR1

The Journal of neuroscience : the official journal of the Society for Neuroscience, 1995

The main excitatory neurotransmitter in the brain, glutamate (Glu), activates not only receptor-c... more The main excitatory neurotransmitter in the brain, glutamate (Glu), activates not only receptor-channels, but also receptors coupled to G-protein called metabotropic Glu receptors (mGluRs). Eight genes coding for mGluRs have been characterized to date giving rise to even more proteins due to alternative splicing phenomena. Here we characterized a splice variant of mGluR5, called mGluR5b which contains a 32 amino acid fragment inserted in the cytoplasmic tail, 50 residues after the 7th transmembrane domain. mGluR5b mRNAs are present in different regions of the adult rat brain and are expressed at a higher level than mGluR5a mRNA. Functional analysis of mGluR5a and mGluR5b revealed that they share all the properties of mGluR1a, but not those of mGluR1b or 1c. Like mGluR1a, both mGluR5a and mGluR5b activate a rapid and transient current in Xenopus oocytes. When expressed in LLC-PK1 cells, they show the same subcellular distribution as mGluR1a, and stimulate both inositol phosphate (IP)...

Research paper thumbnail of Enantioselective synthesis of both enantiomers of the neuroexcitant 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA)

Research paper thumbnail of ChemInform Abstract: An Efficient and General Enantioselective Synthesis of Some Isoxazole-Containing Analogues of the Neuroexcitant Glutamic Acid

Research paper thumbnail of Both enantiomers of 1-aminocyclopentyl-1, 3-dicarboxylate are full agonists of metabotropic glutamate receptors coupled to phospholipase C

Molecular …, 1992

We tested the effects of two enantiomers of a glutamate analogue,(trans)-1-aminocyclopentyl-1, 3-... more We tested the effects of two enantiomers of a glutamate analogue,(trans)-1-aminocyclopentyl-1, 3-dicarboxylate (t-ACPD), in striatal and cerebellar neurons in primary culture, as well as in Xenopus oocytes injected with cerebellar rat RNA. In the presence of ...

Research paper thumbnail of Enantioselective synthesis of both enantiomers of the neuroexcitant 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA)

Tetrahedron: Asymmetry, 2000

Research paper thumbnail of Stereospecific synthesis and absolute configuration of optically active diaryl(acyloxy)(alkoxy)spiro-λ4-sulfanes

Tetrahedron: Asymmetry, 1997

Research paper thumbnail of An efficient and general enantioselective synthesis of some isoxazole-containing analogues of the neuroexcitant glutamic acid

Tetrahedron: Asymmetry, 1998

Research paper thumbnail of Phosphonate analogues of carboxylic acids as aminoacid antagonists on rat cortical neurones

Neuroscience Letters, 1981

Phosphonate analogues of carboxylic acids have been tested as antagonists of excitatory aminoacid... more Phosphonate analogues of carboxylic acids have been tested as antagonists of excitatory aminoacids in rat cerebral cortex. (+/-)--2-Amino-7-phosphono-heptanoic acid and the (-)-D-isomer of the pentanoate derivative were more potent and selective antagonists of N-methyl-D-aspartate (NMDA) than compounds tested previously. The results support the view that a distinct population of receptors exists which are preferentially activated by NMDA.

Research paper thumbnail of Acridinic acid: A new antagonist of amino acid-induced excitations of central neurones

Neuroscience Letters, 1986

The actions of acridinic acid (2,3-quinoline dicarboxylic acid), a new derivative of quinolinic a... more The actions of acridinic acid (2,3-quinoline dicarboxylic acid), a new derivative of quinolinic acid, as an antagonist of amino acid-induced excitations are described. Acridinate, like kynurenate, in the cerebral cortex reduced the effects of all amino acids equally, but in the spinal cord was significantly less active against quisqualate.

Research paper thumbnail of Quinolinate activation of ion channels in rat hippocampal neurons

Neuroscience Letters, 1990

Research paper thumbnail of Methionine sulfoximine shows excitotoxic actions in rat cortical slices

Canadian Journal of Physiology and Pharmacology, 1999

Methionine sulfoximine (MSO) is a rare amino acid. It occurs in nature or as a by-product of some... more Methionine sulfoximine (MSO) is a rare amino acid. It occurs in nature or as a by-product of some forms of food processing. A notable example of the latter was a former method for bleaching wheat flour, using nitrogen trichloride, the "agene process," in use for most of the first 50 years of this century. "Agenized" flour was found to be responsible for various neurological disorders in animals, and MSO was identified as the toxic factor. The agene process was subsequently discontinued in the United States and the United Kingdom circa 1950. MSO inhibits the synthesis of both glutathione and glutamine, and it is possible that its actions on the nervous system arise from alterations in the amount or distribution of these molecules. Structurally, MSO resembles glutamate, an observation that has also raised the possibility that it might have more direct glutamate-like actions on neurons. In the present investigation, we report excitatory and toxic actions of MSO in an in vitro preparation of adult rat cortex. Field potential recordings in this preparation show that MSO application evokes a sustained depolarization, which can be blocked by the N-methyl-D-aspartate (NMDA) antagonist L-(+)-2-amino-5-phosphonovalerate (AP5). However, competition assays using MSO on [3H]CGP-39653 (DL-(E)-2-amino-4-propyl-1-phosphono-3-pentenoate) binding in rat cortical homogenates show only 20% displacement of total binding, suggesting that MSO is acting indirectly, perhaps by releasing glutamate. To investigate this possibility, we measured glutamate release during MSO application. Time course and dose-response experiments with MSO showed significant [3H]glutamate release, which was partially attenuated by AP5. To assess cellular toxicity, we measured lactate dehydrogenase (LDH) release from cortical sections exposed to MSO. MSO treatment led to a rapid increase in LDH activity, which could be blocked by AP5. These data suggest that MSO acts by increasing glutamate release, which then activates NMDA receptors, leading to excitotoxic cell death. These data suggest the possibility that MSO in processed flour had excitotoxic actions that may have been contributing factors to some human neuronal disorders.Key words: agene process, glutamate release, lactate dehydrogenase, methionine sulfoximine, N-methyl-D-aspartate (NMDA) receptor, neurological disorders.

Research paper thumbnail of Characterization of a metabotropic glutamate receptor: direct negative coupling to adenylyl cyclase and involvement of a pertussis toxin-sensitive G protein

Proceedings of the National Academy of Sciences of the United States of America, Sep 1, 1992

Research paper thumbnail of Enantioselective synthesis of both enantiomers of the neuroexcitant 2-amino-3-(3-hydroxy-5- tert -butylisoxazol-4-yl) propanoic acid (ATPA)

Tetrahedron-asymmetry, Dec 1, 2000

Research paper thumbnail of Ca 2+ -dependent depolarization and burst firing of rat CA1 pyramidal neurones induced by N -methyl- D -aspartic acid and quinolinic acid: antagonism by 2-amino-5-phosphonovaleric and kynurenic acids

Canadian Journal of Physiology and Pharmacology, 1986

The excitatory effects of microiontophoretically applied quisqualic (QUIS), N-methyl-D-aspartic (... more The excitatory effects of microiontophoretically applied quisqualic (QUIS), N-methyl-D-aspartic (NMDA), and quinolinic (QUIN) acids were investigated using intracellular recording from CA1 pyramidal neurones in slices of rat hippocampus. QUIS evoked only simple action potentials superimposed upon a depolarization which attained a clear plateau. When this level had been reached, increased ejecting currents did not produce further depolarization. By contrast, with low currents NMD A and QUIN elicited small membrane depolarizations which triggered bursts of action potentials superimposed upon rhythmically occurring depolarizing shifts. Larger currents caused depolarization which if sufficiently large completely blocked spike activity. Tetrodotoxin (TTX) prevented the spikes evoked by QUIS and the bursts of action potentials seen with NMDA and QUIN, and the rhythmic depolarizing shifts then appeared as broad spikes of up to 50 mV in amplitude. These and the underlying membrane depolariz...

Research paper thumbnail of MOLECULAR PHARMACOLOGY, 42:322-327 Both Enantiomers of 1-Aminocyclopentyl-1,3-.dicarboxylate Are Full Agonists of Metabotropic Glutamate Receptors Coupled to

We tested the effects of two enantiomers of a glutamate ana-

Research paper thumbnail of Psychiatric Drug Discovery and Development--SRI's Third Annual Conference

Research paper thumbnail of Single channel properties of the N-methyl-D-aspartate receptor channel using NMDA and NMDA agonists: on-cell recordings

Experimental Brain Research

Research paper thumbnail of The actions of a conformationally restricted analogue of aspartic acid on mammalian spinal neurones

Neuroscience Letters

ABSTRACT

Research paper thumbnail of Synthesis, resolution, and absolute configuration of the isomers of the neuronal excitant 1-amino-1,3-cyclopentanedicarboxylic acid

Journal of Medicinal Chemistry

Research paper thumbnail of Psychiatric Drug Discovery and Development--SRI's Third Annual Conference

IDrugs : the investigational drugs journal, 2005

Research paper thumbnail of Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants: comparison with mGluR1

The Journal of neuroscience : the official journal of the Society for Neuroscience, 1995

The main excitatory neurotransmitter in the brain, glutamate (Glu), activates not only receptor-c... more The main excitatory neurotransmitter in the brain, glutamate (Glu), activates not only receptor-channels, but also receptors coupled to G-protein called metabotropic Glu receptors (mGluRs). Eight genes coding for mGluRs have been characterized to date giving rise to even more proteins due to alternative splicing phenomena. Here we characterized a splice variant of mGluR5, called mGluR5b which contains a 32 amino acid fragment inserted in the cytoplasmic tail, 50 residues after the 7th transmembrane domain. mGluR5b mRNAs are present in different regions of the adult rat brain and are expressed at a higher level than mGluR5a mRNA. Functional analysis of mGluR5a and mGluR5b revealed that they share all the properties of mGluR1a, but not those of mGluR1b or 1c. Like mGluR1a, both mGluR5a and mGluR5b activate a rapid and transient current in Xenopus oocytes. When expressed in LLC-PK1 cells, they show the same subcellular distribution as mGluR1a, and stimulate both inositol phosphate (IP)...

Research paper thumbnail of Enantioselective synthesis of both enantiomers of the neuroexcitant 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA)

Research paper thumbnail of ChemInform Abstract: An Efficient and General Enantioselective Synthesis of Some Isoxazole-Containing Analogues of the Neuroexcitant Glutamic Acid

Research paper thumbnail of Both enantiomers of 1-aminocyclopentyl-1, 3-dicarboxylate are full agonists of metabotropic glutamate receptors coupled to phospholipase C

Molecular …, 1992

We tested the effects of two enantiomers of a glutamate analogue,(trans)-1-aminocyclopentyl-1, 3-... more We tested the effects of two enantiomers of a glutamate analogue,(trans)-1-aminocyclopentyl-1, 3-dicarboxylate (t-ACPD), in striatal and cerebellar neurons in primary culture, as well as in Xenopus oocytes injected with cerebellar rat RNA. In the presence of ...

Research paper thumbnail of Enantioselective synthesis of both enantiomers of the neuroexcitant 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA)

Tetrahedron: Asymmetry, 2000

Research paper thumbnail of Stereospecific synthesis and absolute configuration of optically active diaryl(acyloxy)(alkoxy)spiro-λ4-sulfanes

Tetrahedron: Asymmetry, 1997

Research paper thumbnail of An efficient and general enantioselective synthesis of some isoxazole-containing analogues of the neuroexcitant glutamic acid

Tetrahedron: Asymmetry, 1998

Research paper thumbnail of Phosphonate analogues of carboxylic acids as aminoacid antagonists on rat cortical neurones

Neuroscience Letters, 1981

Phosphonate analogues of carboxylic acids have been tested as antagonists of excitatory aminoacid... more Phosphonate analogues of carboxylic acids have been tested as antagonists of excitatory aminoacids in rat cerebral cortex. (+/-)--2-Amino-7-phosphono-heptanoic acid and the (-)-D-isomer of the pentanoate derivative were more potent and selective antagonists of N-methyl-D-aspartate (NMDA) than compounds tested previously. The results support the view that a distinct population of receptors exists which are preferentially activated by NMDA.

Research paper thumbnail of Acridinic acid: A new antagonist of amino acid-induced excitations of central neurones

Neuroscience Letters, 1986

The actions of acridinic acid (2,3-quinoline dicarboxylic acid), a new derivative of quinolinic a... more The actions of acridinic acid (2,3-quinoline dicarboxylic acid), a new derivative of quinolinic acid, as an antagonist of amino acid-induced excitations are described. Acridinate, like kynurenate, in the cerebral cortex reduced the effects of all amino acids equally, but in the spinal cord was significantly less active against quisqualate.

Research paper thumbnail of Quinolinate activation of ion channels in rat hippocampal neurons

Neuroscience Letters, 1990