Endogenous Amino Acid Neurotransmitters Research Articles

Role of Prostanoid Production and Receptors in the Regulation of Retinal Endogenous Amino Acid Neurotransmitters by 8-Isoprostaglandin E2, Ex Vivo

The role of enzymes and receptors of the prostanoid pathway in the inhibitory effect of 8-isoprostaglandin E2 (8-isoPGE2) on endogenous amino acid neurotransmitter levels was examined, ex vivo. Freshly isolated bovine eyeballs were injected intravitreally with IsoPs, incubated in Krebs buffer for 30 min and retina prepared for HPLC-ECD detection of amino acids. 8-isoPGE2 attenuated retinal glutamate and its metabolite, glutamine and glycine in a concentration-dependent manner. The nonselective cyclooxygenase (COX)-inhibitor, flurbiprofen, COX-2 selective inhibitor, NS-398 and thromboxane (Tx) synthase inhibitor, furegrelate had no effect on both basal amino acid levels and the inhibitory effects of 8-isoPGE2 (1-100 μM) on the retinal amino acids. Whereas the TP-receptor antagonist SQ-29548(10 μM) exhibited no effect, SC-19220(EP1; 30 μM), AH-6809(EP(1-3); 30 μM) and AH-23848(EP4; 30 μM) reversed the inhibitory effects of 8-isoPGE2 (0.01-100 μM) on glutamate, glutamine and glycine levels. We conclude that prostanoid EP-receptors regulate the inhibitory effect of 8-isoPGE2 on basal levels of endogenous amino acids in bovine retina, ex vivo.

Extracellular perfusion of rat brain nuclei using microdialysis: a method for studying differential neurotransmitter release in response to neurotoxins

Microdialysis probes, stereotactically placed in rat brain nuclei, allow detailed kinetic comparisons of neurotransmitter release from in situ chemical lesioning over a continuum from acute early changes (minutes) to chronic late changes (days). This technique insures a localized mechanism of action independent of systemic effects apparent with other routes of administration and independent of mechanical damage patterns encountered in conventional chemical lesioning. The example provided compares changes in extracellular γ-aminobutyric acid (GABA) concentrations in the striatum in response to quinolinic acid (QA, 0.24 M) and 3-nitropropionic acid (3-NPA, 0.25 M). These examples of chemical lesioning represent two theoretical mechanisms of neurodeterioration in Huntington's disease, QA representing the excitotoxic component, and 3-NPA representing the impaired mitochondrial energy component [M.F. Beal, N.W. Kowall, D.W. Ellison, M.F. Mazurek, K.J. Swartz, J.M. Martin, Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid, Nature 321 (1986) 168–171; M.F. Beal, E. Brouillet, B.G. Jenkins, R.J. Ferrante, N.W. Kowall, J.M. Miller, E. Storey, R. Srivastava, B.R. Rosen, B.T. Hyman, Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 13 (1993) 4181–4192; N.C. Reynolds, W. Lin, C.M. Cameron, D.L. Roerig, Differential responses of extracellular GABA to intrastriatal perfusions of 3-nitropropionic acid and quinolinic acid in the rat, Brain Res. 778 (1997) 140–149]. An auxillary microdialysis probe implanted in the ipsilateral nucleus accumbens is used to define the physiologic extent of the cytotoxic lesion. Pre-column derivatization of perfusate fractions with o-phthalaldehyde/ t-butylthiol (OPA) provides electroactivity to the OPA-GABA conjugate and facilitates electrochemical detection following high performance liquid chromatography [J.M. Peinado, K.T. McManus, R.B. Myers, Rapid method for microanalysis of endogenous amino acid neurotransmitters in brain perfusates in the rat by isocratic HPLC-EC, J. Neurosci. Methods 18 (1986) 269–276]. Theme: Disorders of the nervous system Topic: Degenerative disease: other

Effect of various depolarizing agents on endogenous amino acid neurotransmitter release in rat cortical neurons in culture

The purpose of this study is to determine whether differences in membrane potential and/or intracellular Ca 2+ increments are implicated in a programmed release of amino acid neurotransmitters (aspartate, glutamate, glycine and GABA) in cortical neurons in culture. According to our results, it is possible to assume that difference in membrane potential is not the only signal which starts the amino acid neurotransmitter release, but there are other necessary conditions at the start of this amino acid release. One of these conditions could be the increment in intracellular Ca 2+, but our results indicate that, in cortical neurons in culture, the total intracellular Ca 2+ increments are not important on release levels, but are the stimulating agent which produces this intracellular Ca 2+ increment. From these results we may infer: (1) that in rat cortical neurons there are neurons which contain and release glutamate, aspartate, glycine and GABA, (2) that in cortical neurons the 36.6±5.8% of the neurons are GABA-ergic, (3) that the membrane potential and the total intracellular calcium are not only responsible for the release of these amino acids but also the depolarizing agent which plays an important role in this release, and (4) that glutamate and aspartate and glutamate and GABA are localized in different vesicular pools or in different cell neurons.

Desyl Esters of Amino Acid Neurotransmitters. Phototriggers for Biologically Active Neurotransmitters

The application of the desyl or 2-oxo-1,2-diphenylethyl moiety as a photolabile ligand for the release of phosphates such as cAMP and inorganic phosphate (Pi)1,2 is extended to include selected excitatory amino acids. The synthesis and photochemical studies of N- and O-desyl-caged versions of the endogenous amino acid neurotransmitters glutamate and γ-aminobutyric acid (GABA) are reported. Photolysis at 350 nm of solutions of γ-O-desyl glutamate (11) and O-desyl GABA (14) in 1:1 H2O−acetonitrile cleanly produced free glutamate and GABA, respectively, with rate constants of ca. 107 s-1; 2-phenylbenzo[b]furan (2) was the only photobyproduct detected by HPLC. Photolysis quantum efficiencies for the disappearance of O-desyl amino acid esters were in the range of 0.29−0.31, and the appearance efficiencies of furan 2 (and the corresponding amino acid) were 0.14. The photolysis of 14 was efficiently quenched with sodium 2-naphthalenesulfonate, yielding a triplet lifetime of ca. 10 ns. Photolysis of 11 in mammali...

LTP in the dentate gyrus is associated with a persistent NMDA receptor-dependent enhancement of synaptosomal glutamate release

LTP was induced unilaterally in the dentate gyrus of the anaesthetized rat by tetanic stimulation of the perforant path. Two hours after tetanization synaptosomes were prepared from control and potentiated sides, and the depolarization-induced release of endogenous amino acid neurotransmitters was compared in the two groups, using 4-aminopyridine, potassium or veratridine as depolarizing agents. Glutamate release was greater in synaptosomes from potentiated than control tissue with all three depolarizing agents, but the highest release from control synaptosomes and the most significant enhancement of release from potentiated synaptosomes was seen with veratridine. The tetanus-induced enhancement of veratridine-induced glutamate release was prevented by pretreatment with MK-801. The results indicate that the induction of LTP in the dentate gyrus is accompanied by a persistent enhancement in the ability of synaptosomes to release glutamate in response to a depolarizing stimulus.

The effects of sigma ligands on the release of glutamate from rat striatal slices

This study investigated the effects of sigma receptor ligands on the release of endogenous amino acid neurotransmitters from rat striatal slices. The effect of haloperidol on release in slices prepared from 6-hydroxydopamine lesioned animals was also tested. Haloperidol, the (+/-) reduced metabolite of haloperidol, rimcazole and ifenprodil specifically reduced potassium-stimulated release of glutamate with IC50 values between 20-60 microM. The release of aspartate, gamma-aminobutyric acid (GABA) and glycine was not affected. Haloperidol also reduced glutamate release from slices prepared from lesioned animals. The neuroleptic drug alpha-flupenthixol and the putative sigma receptor ligand R(+)3-(3-hydroxyphenyl)-N-(n-propyl) piperidine (3-PPP) had no effect on release. These effects of the sigma ligands show that the inhibition of glutamate release is specific to this amino acid and also that it is not due to dopamine receptor blockade as those ligands which have low affinity for dopamine receptors were also effective in reducing release. A presynaptic location for sigma receptor sites, possibly associated with ion channels, could account for the effects of these ligands on transmitter release.

Specific increases in the overflow of endogenous amino acid neurotransmitter candidates from the medulla in vivo: a microdialysis study : V. Kapoor, D. Nakahara, A. Piekarz, R.J. Blood and J.P. Chalmers Department of Medicine and Centre for Neuroscience, Flinders Medical Centre, Bedford Park, South Australia 5042

Specific increases in the overflow of endogenous amino acid neurotransmitter candidates from the medulla in vivo: a microdialysis study : V. Kapoor, D. Nakahara, A. Piekarz, R.J. Blood and J.P. Chalmers Department of Medicine and Centre for Neuroscience, Flinders Medical Centre, Bedford Park, South Australia 5042

Hemidecortication selectively alters release of glutamate in perfusates collected from cerebral cortex of unrestrained rats.

The effect of hemidecortication on the in vivo release of amino acids was examined in different areas of the cerebral cortex of the freely-moving rat. After one side of the cortex was lesioned by aspiration, four guide tubes for push-pull perfusion were implanted chronically on the contralateral side so as to rest above the frontal, parietal, temporal and occipital areas of the cortex. After 10-14 days elapsed, each of these regions was perfused with an artificial cerebrospinal fluid (CSF) at a rate of 25.0 microliter/min. Two types of assays were undertaken to determine the release of either newly synthesized amino acids from [14C]glucose precursor or the actual endogenous content in samples of perfusate. The separation of the [14C]amino acids was performed by thin layer chromatography, whereas endogenous amino acids were separated by HPLC with electrochemical detection and quantitated in the range of 1.0-10.0 picomoles. When compared to the control group, samples collected in the hemidecorticate rat showed no significant differences in the new synthesis of glutamate, aspartate, glutamine, glycine, and GABA from the precursor. On the other hand, the analysis of the endogenous amino acid neurotransmitters revealed that the levels of glutamic acid and glutamine declined in samples obtained from the parietal and frontal cortex, respectively. These results implicate further the potential role of glutamic acid as a neurotransmitter of interhemispheric connections in the cerebral cortex.

Rapid method for micro-analysis of endogenous amino acid neurotransmitters in brain perfusates in the rat by isocratic HPLC-EC

A simplified method is described for the isocratic analysis of endogenous amino acid neurotransmitters contained in brain perfusates by high performance liquid chromatography (HPLC) with electrochemical detection (EC). Pre-column o-phthalaldehyde (OPA) tert-butylthiol derivatives of the amino acids were injected into a C 18 3 μm column. After linear concentration curves for standard solutions were obtained, the content of 6 amino acid neurotransmitters was analyzed in push-pull perfusates obtained from the hypothalamus and cerebral cortex of the unrestrained rat. Each analysis which included the simultaneous quantification of aspartic acid, glutamic acid, glutamine, glycine, taurine and γ-aminobutyric acid (GABA), was completed in less than 15 min. The sensitivity of the assay ranged from 1.0 to 5.0 pmol of each amino acid contained within a 20 μ1 aliquot of each perfusion sample.

Baclofen: Effects on evoked field potentials and amino acid neurotransmitter release in the rat olfactory cortex slice

A study has been made of the in vitro effects of (±)- and (−)-baclofen on the evoked field potentials and release of endogenous amino acid neurotransmitter candidates (aspartate, glutamate, GABA and possibly taurine) which accompany electrical stimulation of the excitatory input to the olfactory cortex slice, the lateral olfactory tract. Baclofen appears to reduce the excitatory input to the GABA-utilizing inhibitory interneurones; this action was manifest as a drug-induced abolition of the field potential known as the P-wave (IC 50 for (−)-baclofen, 1.7±0.4 μM) together with a simultaneous reduction in the synaptically evoked release of aspartate and glutamate from the cut surface of slices. Both these actions of baclofen exhibited concentration dependence and stereospecificity and were not antagonized by pictotoxin (25 μM) thereby suggesting that they are directly related. The consequence of this action of baclofen was the abolition of GABA-mediated presynpatic and postsynaptic inhibition together with their respective field potential correlates, the late N- and I- waves. (±)-Baclofen (5 and 25 μM) also inhibited the potassium-evoked release of aspartate and glutamate from small cubes of tissue but, except at a high concentration (1 mM), had no effect on GABA release. Baclofen (up to 1 mM) did not affect transmission either at the lateral olfactory tract-superficial pyramidal cell synapse, a site where aspartate is the likely neurotransmitter 9–16, or at the superficial pyramidal cell collateral-deep pyramidal cell excitatory synapse. It is proposed that: (i) the actions of baclofen on the olfactory cortex are the result of inhibition of aspartate and glutamate release, probably from deep pyramidal cell collaterals; and (ii) not all neurones utilizing excitatory amino acids as their neurotransmitters are subject to the inhibitory action of baclofen.

Aspartate and not glutamate is the likely transmitter of the rat lateral olfactory tract fibres

The protoveratrine A-evoked release of endogenous amino acid neurotransmitter candidates from olfactory cortex slices taken from control and bulbectomized rats has been monitored. Bulbectomy is accompanied by a statistically significant and specific attenuation of drug-evoked aspartate release suggesting that the excitatory transmitter of the lateral olfactory tract fibres is aspartate rather than glutamate.

Patterns of endogenous amino acid release from slices of rat and guinea-pig olfactory cortex

A study has been made of the effects of depolarizing stimuli on the release of endogenous amino acid neurotransmitter candidates (aspartate, glutamate, GABA and taurine) from in vitro preparations of rat and guinea pig olfactory cortex. Exposure of small cubes of olfactory cortex tissue from either species to potassium chloride (50 mM) was accompanied by a calcium-dependent release of aspartate, glutamate and GABA. A similar release pattern was evoked by protoveratrine A (100 muM) although the release was largely calcium-independent. Neither agent led to increased release of taurine. Electrical stimulation of the excitatory input (lateral olfactory tract) of freshly prepared, synaptically intact olfactory cortex slices of both species induced significant release of aspartate and GABA from the uncut pial surface and of aspartate, GABA and glutamate from the cut surface. Evoked taurine release occurred from both surfaces of rat olfactory cortex slices but no release was detected from guinea pig olfactory cortex slices. These patterns of release were unaffected by changes in stimulus frequency and were mimicked by protoveratrine A (100 muM) applied to one or other surface. Preincubation of slices from rats for 2 led to loss of tissue amino acids and to changes in their release patterns; the presence of glutamine (5 mM) during preincubation prevented the loss of amino acids but did not alter their pattern of release. Because of the close similarities between both the electrophysiological properties and the patterns of amino acid release it is concluded that there is probably an identity of amino acid neurotransmitters (aspartate, glutamate and GABA) in rat and guinea pig olfactory cortex. The role of taurine in the rat olfactory cortex is unknown but would seem unlikely to be that of a neurotransmitter. The results are discussed: (i) in terms of the cellular origins of the released amino acids; and (ii) wit respect to apparent experimental discrepancies which have appeared in the literature.

Release of endogenous amino acid neurotransmitter candidates from rat olfactory cortex slices: Possible regulatory mechanisms and the effects of pentobarbitone

A study has been made of the regulation of evoked release of the amino acid neurotransmitter candidates (aspartate, GABA and taurine) from rat olfactory cortex slices. The effects of pentobarbitone (10–1000 μM) on release have also been assessed. Release of aspartate, the presumed excitatory transmitter of some of the lateral olfactory tract fibres, is reduced by muscimol (10 μM) and this effect is antagonized by picrotoxin (15 μM): it is concluded that presynaptic GABA receptors may modulate aspartate release. Low concentrations of pentobarbitone also reduce aspartate release, but this effect is picrotoxin-insensitive. Release of GABA, the presumed transmitter of inhibitory interneurones, is reduced by muscimol (10 μM) and this effect is antagonized by picrotoxin (15 μM): it is suggested that GABA release may be regulated by presynaptic autoreceptors. Pentobarbitone significantly increases release of GABA when slices are synaptically activated although the mechanism of this effect is nuclear. Release of taurine, not hitherto considered a neurotransmitter in this brain area, is depressed by muscimol (10 μM) and pentobarbitone and increased by picrotoxin (15 μM). Results are discussed in terms of (i) mechanisms of regulation of amino acid release in the olfactory cortex, (ii) effects of pentobarbitone on release and(iii) the compatibility of the present results with previously published electrophysiological studies.

Current-density analysis of summed evoked potentials in opossum prepyriform cortex.

Current-density analysis of summed evoked potentials in opossum prepyriform cortex.

Unitary analysis of opossum prepyriform cortex.

Unitary analysis of opossum prepyriform cortex.L B HaberlyL B HaberlyPublished Online:01 Jul 1973https://doi.org/10.1152/jn.1973.36.4.762MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByOdor-Driven Activity in the Olfactory Cortex of an In Vitro Isolated Guinea Pig Whole Brain With Olfactory EpitheliumTakahiro Ishikawa, Takaaki Sato, Akira Shimizu, Ken-Ichiro Tsutsui, Marco de Curtis, and Toshio Iijima1 January 2007 | Journal of Neurophysiology, Vol. 97, No. 1Variable Coupling Between Olfactory System Activity and Respiration in Ketamine/Xylazine Anesthetized RatsAlfredo Fontanini, and James M. Bower1 June 2005 | Journal of Neurophysiology, Vol. 93, No. 6Convergence of Multimodal Sensory Input Onto Higher-Level Neurons of the Crayfish Olfactory PathwayDeForest Mellon1 December 2000 | Journal of Neurophysiology, Vol. 84, No. 6Time Course of Odorant-Induced Activation in the Human Primary Olfactory CortexNoam Sobel, Vivek Prabhakaran, Zuo Zhao, John E. Desmond, Gary H. Glover, Edith V. Sullivan, and John D. E. Gabrieli1 January 2000 | Journal of Neurophysiology, Vol. 83, No. 1Duration of NMDA-Dependent Synaptic Potentiation in Piriform Cortex In Vivo Is Increased After Epileptiform BurstingA. Kapur, and L. B. Haberly1 October 1998 | Journal of Neurophysiology, Vol. 80, No. 4GABAA-Mediated IPSCs in Piriform Cortex Have Fast and Slow Components With Different Properties and Locations on Pyramidal CellsA. Kapur, R. A. Pearce, W. W. Lytton, and L. B. Haberly1 November 1997 | Journal of Neurophysiology, Vol. 78, No. 5Characterization and anatomical distribution of selective long-term potentiation in the olfactory forebrainBrain Research, Vol. 542, No. 1Effects of NMDA antagonists, MK-801 and CPP, upon local cerebral glucose useBrain Research, Vol. 496, No. 1-2Selective long-term potentiation in the pyriform cortexBrain Research, Vol. 441, No. 1-2Evidence for synaptic potentiation in a cortical network during learningBrain Research, Vol. 418, No. 2Relation of olfactory bulb and cortex. I. Spatial variation of bulbocortical interdependenceBrain Research, Vol. 409, No. 2Relation of olfactory bulb and cortex. II. Model for driving of cortex by bulbBrain Research, Vol. 409, No. 2Effect of olfactory bulb kindling on evoked potentials in the pyriform cortexBrain Research, Vol. 361, No. 1-2Spatial EEG patterns, non-linear dynamics and perception: the neo-sherringtonian viewBrain Research Reviews, Vol. 10, No. 3Current generators and properties of early components evoked in rat olfactory cortexBrain Research Bulletin, Vol. 15, No. 3Excitatory and inhibitory effects of dopamine on synaptic transmission in the rat olfactory cortex sliceBrain Research, Vol. 333, No. 2Excitatory and inhibitory effects of noradrenaline on synaptic transmission in the rat olfactory cortex sliceBrain Research, Vol. 294, No. 2Monosynaptic and disynaptic activation of pyriform cortex neurons by synchronous lateral olfactory tract volleys in the rabbitExperimental Neurology, Vol. 81, No. 3Cytoarchitecture of the nucleus of the lateral olfactory tract: A Golgi study in the ratBrain Research Bulletin, Vol. 10, No. 4Baclofen: Effects on evoked field potentials and amino acid neurotransmitter release in the rat olfactory cortex sliceBrain Research, Vol. 238, No. 2The effects of chlordiazepoxide on synaptic transmission and amino acid neurotransmitter release in slices of rat olfactory cortexBrain Research, Vol. 224, No. 2Aspartate and not glutamate is the likely transmitter of the rat lateral olfactory tract fibresBrain Research, Vol. 209, No. 1Patterns of endogenous amino acid release from slices of rat and guinea-pig olfactory cortexBrain Research, Vol. 204, No. 1Release of endogenous amino acid neurotransmitter candidates from rat olfactory cortex slices: Possible regulatory mechanisms and the effects of pentobarbitoneBrain Research, Vol. 190, No. 2Depolarization of neurones in slices of the olfactory cortex of the guinea-pig by GABABrain Research Bulletin, Vol. 5The distribution of olfactory input in the opossum mediodorsal nucleusBrain Research, Vol. 138, No. 2The axonal projection patterns of the mitral and tufted cells of the olfactory bulb in the ratBrain Research, Vol. 129, No. 1Antidromic units in the prepyriform cortex driven by olfactory peduncular volleysBrain Research, Vol. 92, No. 1 More from this issue > Volume 36Issue 4July 1973Pages 762-74 https://doi.org/10.1152/jn.1973.36.4.762PubMed4713318History Published online 1 July 1973 Published in print 1 July 1973 Metrics

Summed potentials evoked in opossum prepyriform cortex.

Summed potentials evoked in opossum prepyriform cortex.