Biochemistry and Physiology of Amino Acid Transmitters

Obata, Kunihiko

doi:10.1002/cphy.cp010117

Cited by 14 publications

(5 citation statements)

References 359 publications

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“…IT IS WELL ESTABLISHED that glutamate is released at excitatory synapses and acts as a neurotransmitter in the central nervous system (6,57). On its release at central synapses, glutamate acts at excitatory amino acid receptors and mediates responses through phosphoinositide hydrolysis, intracellular calcium mobilization, and neuronal depolarization via activation of intracellular second messenger systems (21,22,63).…”

Section: Baroreflex; Ionotropic Receptormentioning

confidence: 99%

NMDA receptors in nucleus tractus solitarii are linked to soluble guanylate cyclase

Chianca¹,

Lin²,

Dragon³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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We sought to test the hypothesis that cardiovascular responses to activation of ionotropic, but not metabotropic, glutamate receptors in the nucleus tractus solitarii (NTS) depend on soluble guanylate cyclase (sGC) and that inhibition of sGC would attenuate baroreflex responses to changes in arterial pressure. In adult male Sprague-Dawley rats anesthetized with chloralose, the ionotropic receptor agonists N-methyl-d-aspartate (NMDA) and dl-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and the metabotropic receptor agonist trans-dl-amino-1,3-cyclopentane-dicarboxylic acid (ACPD) were microinjected into the NTS before and after microinjection of sGC inhibitors at the same site. Inhibition of sGC produced significant dose-dependent attenuation of cardiovascular responses to NMDA but did not alter responses produced by injection of AMPA or ACPD. Bilateral inhibition of sGC did not alter arterial pressure, nor did it attenuate baroreflex responses to pharmacologically induced changes in arterial pressure. This study links sGC with NMDA, but not AMPA or metabotropic, receptors in cardiovascular signal transduction through NTS.

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Section: Baroreflex; Ionotropic Receptormentioning

confidence: 99%

NMDA receptors in nucleus tractus solitarii are linked to soluble guanylate cyclase

Chianca¹,

Lin²,

Dragon³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…GAD65 -/mice provide a valuable tool to further dissect the GABAergic mechanisms involved in fear and anxiety and to model GABArelated neurological and psychiatric disorders. g-Aminobutyric acid (GABA), the major inhibitory neurotransmitter of the mammalian brain, is involved in diverse neural functions ranging from development and neural plasticity to the control of motor behavior and emotion (Obata 1977). Specificity of GABA functions in the brain is achieved in part through a structural and neurochemical heterogeneity of GABA neurons and a variety of GABA receptors.…”

mentioning

confidence: 99%

Altered conditioned fear behavior in glutamate decarboxylase 65 null mutant mice

Stork

Yamanaka

Stork

et al. 2003

Genes Brain and Behavior

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We investigated the involvement of the 65 kDa isoform of glutamic acid decarboxylase (GAD65) and GAD65-mediated g -aminobutyric acid (GABA) synthesis in the formation and expression of Pavlovian fear memory. To this end, behavioral, endocrine and autonomic parameters were examined during conditioned fear retrieval of mice with targeted ablation of the GAD65 gene (GAD65 -/-mice). These mutant mice were found to display specific fear behavior (freezing, escape), as well as autonomic (increased defecation) and endocrine activation (increased plasma corticosterone) during fear memory retrieval. However, freezing was reduced and flight and escape behavior were increased in GAD65 -/-mice compared to their wild type and heterozygous littermates, while corticosterone levels and defecation rates did not differ between genotypes. Active defensive behavior of GAD65 -/-mice was observed during both auditory cued and contextual retrieval of fear memory, as well as immediately after conditioning. These data indicate a selectively altered behavioral fear response in GAD65 -/-mice, most likely due to deficits in threat estimation or the elicitation of appropriate conditioned fear behavior, and suggest that GAD65 is a genetic determinant of conditioned fear behavior. GAD65 -/-mice provide a valuable tool to further dissect the GABAergic mechanisms involved in fear and anxiety and to model GABArelated neurological and psychiatric disorders.

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“…In the spinal cord, and several other regions of the central nervous system, glycine is involved in inhibitory synaptic transmission (20); it produces an increase of the postsynaptic chloride conductance (32) and this effect is selectively antagonized by strychnine (20). Recently, the glycine receptor was solubilized in the presence of detergent (22) and after purification on a strychnine affinity column, shown to be an oligomeric glycoprotein with a total molecular weight of 246,000 ___ 6,000 (23).…”

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confidence: 99%

Distribution of glycine receptors at central synapses: an immunoelectron microscopy study.

Triller¹,

Cluzeaud²,

Pfeiffer³

et al. 1985

The Journal of Cell Biology

354

230

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The distribution of receptors for a neurotransmitter was investigated cytochemically for the first time in the central nervous system, at synapses established on cells of the ventral horn of the rat cervical spinal cord. Three monoclonal antibodies (mAb's) raised against glycine receptors were used. Immunofluorescent staining already showed discontinuous labeling at the surface of neurons, and immunoenzymatic electron microscopy further revealed that the antigenic determinants were confined to the postsynaptic membrane and concentrated at the level of the synaptic complex. More specifically, one mAb directed against the receptive subunit of the oligomeric receptor recognized an epitope on the extracetlular side of the plasma membrane, whereas two other mAb's bound to the cytoplasmic face. Epitopes for the last two mAb's were more accurately localized with protein A-colloidal gold, using an intermediate rabbit anti-mouse immunoglobulin serum. (a) In addition to the presence of gold particles in areas facing the presynaptic active zone (visualized with ethanolic phosphotungstic acid), the labeling extended beyond this zone for ~50-60 nm, which corresponds to the width of one presynaptic dense projection. (b) The distances between the mid membrane and the gold particles were different for the two mAb's (with means of 21.7 + 8.5 nm and 29.8 + 10.4 nm, respectively). The data suggest that one of the recognized epitopes is close to the plasma membrane, whereas the second protrudes into the cytoplasm. Our results indicate that the receptor is a transmembrane protein which has a restricted spatial distribution on the postsynaptic neuronal surface.Little is known about the organization of receptors for neurotransmitters at central synapses, owing, primarily to the lack of specific high-affinity ligands. In the peripheral nervous system, a-bungarotoxin has been used as a cytochemical marker for acetylcholine receptors localized at the endplate (15, 16). Thus, in the central nervous system, the regional distribution of receptors has only been studied, using agonistic substances, either by light microscopy autoradiography (e.g., for opioid receptors [1 ]) or by electron microscopy, as in the case of opiate (11), benzodiazepine (18), and muscarinic cholinergic (14) receptors. Despite a statistical analysis of the distribution of reduced silver grains, the precise distribution of the labeled molecules with respect to the plasma membrane was difficult to assess due to limitations of the autoradiographic technique. We show in this paper that a direct determination of receptor's distribution, such as that for glycine, is now possible with the help of immunochemistry.In the spinal cord, and several other regions of the central nervous system, glycine is involved in inhibitory synaptic transmission (20); it produces an increase of the postsynaptic chloride conductance (32) and this effect is selectively antagonized by strychnine (20). Recently, the glycine receptor was solubilized in the presence of detergent (22) and aft...

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Biochemistry and Physiology of Amino Acid Transmitters

Cited by 14 publications

References 359 publications

NMDA receptors in nucleus tractus solitarii are linked to soluble guanylate cyclase

NMDA receptors in nucleus tractus solitarii are linked to soluble guanylate cyclase

Altered conditioned fear behavior in glutamate decarboxylase 65 null mutant mice

Distribution of glycine receptors at central synapses: an immunoelectron microscopy study.

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