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Mario Patrizio - One of the best experts on this subject based on the ideXlab platform.

  • astrocyte heterogeneity endogenous amino acid levels and release evoked by non n methyl d aspartate Receptor Agonists and by potassium induced swelling in type 1 and type 2 astrocytes
    Journal of Neurochemistry, 1992
    Co-Authors: Giulio Levi, Mario Patrizio
    Abstract:

    : The aim of the present study was to determine whether endogenous amino acids are released from type-1 and type-2 astrocytes following non-N-methyl-D-aspartate (NMDA) Receptor activation and whether such release is related to cell swelling. Amino acid levels and release were measured by HPLC in secondary cultures from neonatal rat cortex, highly enriched in type-1 or type-2 astrocytes. The following observations were made. (a) The endogenous level of several amino acids (glutamate, alanine, glutamine, asparagine, taurine, serine, and threonine) was substantially higher in type-1 than in type-2 astrocytes. (b) The spontaneous release of glutamine and taurine was higher in type-1 than in type-2 astrocytes; that of other amino acids was similar. (c) Exposure of type-2 astrocyte cultures to 50 microM kainate or quisqualate doubled the release of glutamate and caused a lower, but significant increase in that of aspartate, glycine, taurine, alanine, serine (only in the case of kainate), and glutamine (only in the case of quisqualate). These effects were reversed by the antagonist CNQX. (d) Exposure of type-1 astrocyte cultures to 50-200 microM kainate or 50 microM quisqualate did not affect endogenous amino acid release, even after treating the cultures with dibutyryl cyclic AMP. (e) Exposure of type-1 or type-2 astrocyte cultures to 50 mM KCl (replacing an equimolar concentration of NaCl) enhanced the release of taurine greater than glutamate greater than aspartate. The effect was somewhat more pronounced in type-2 than in type-1 astrocytes. Veratridine (50 microM) did not cause any increase in amino acid release. (f) The release of amino acids induced by high [K+] appeared to be related to cell swelling, in both type-1 and type-2 astrocytes. Swelling and K(+)-induced release were somewhat higher in type-2 than in type-1 astrocytes. In contrast, neither kainate nor quisqualate caused any appreciable increase in cell volume. It is concluded that non-NMDA Receptor Agonists stimulate the release of several endogenous amino acids (some of which are neuroactive) from type-2 but not from type-1 astrocytes. The effect does not seem to be related to cell swelling, which causes a different release profile in both type-1 and type-2 astrocytes. The absence of kainate- and quisqualate-evoked release in type-1 astrocytes suggests that the density of non-NMDA Receptors in this cell type is very low.

  • Astrocyte Heterogeneity: Endogenous Amino Acid Levels and Release Evoked by Non‐N‐Methyl‐D‐Aspartate Receptor Agonists and by Potassium‐Induced Swelling in Type‐1 and Type‐2 Astrocytes
    Journal of Neurochemistry, 1992
    Co-Authors: Giulio Levi, Mario Patrizio
    Abstract:

    : The aim of the present study was to determine whether endogenous amino acids are released from type-1 and type-2 astrocytes following non-N-methyl-D-aspartate (NMDA) Receptor activation and whether such release is related to cell swelling. Amino acid levels and release were measured by HPLC in secondary cultures from neonatal rat cortex, highly enriched in type-1 or type-2 astrocytes. The following observations were made. (a) The endogenous level of several amino acids (glutamate, alanine, glutamine, asparagine, taurine, serine, and threonine) was substantially higher in type-1 than in type-2 astrocytes. (b) The spontaneous release of glutamine and taurine was higher in type-1 than in type-2 astrocytes; that of other amino acids was similar. (c) Exposure of type-2 astrocyte cultures to 50 μM kainate or quisqualate doubled the release of glutamate and caused a lower, but significant increase in that of aspartate, glycine, taurine, alanine, serine (only in the case of kainate), and glutamine (only in the case of quisqualate). These effects were reversed by the antagonist CNQX. (d) Exposure of type-1 astrocyte cultures to 50–200 μM kainate or 50 μM quisqualate did not affect endogenous amino acid release, even after treating the cultures with dibutyryl cyclic AMP. (e) Exposure of type-1 or type-2 astrocyte cultures to 50 mM KCl (replacing an equimolar concentration of NaCl) enhanced the release of taurine > glutamate > aspartate. The effect was somewhat more pronounced in type-2 than in type-1 astrocytes. Veratridine (50 μM) did not cause any increase in amino acid release. (f) The release of amino acids induced by high [K+] appeared to be related to cell swelling, in both type-1 and type-2 astrocytes. Swelling and K+-induced release were somewhat higher in type-2 than in type-1 astrocytes. In contrast, neither kainate nor quisqualate caused any appreciable increase in cell volume. It is concluded that non-NMDA Receptor Agonists stimulate the release of several endogenous amino acids (some of which are neuroactive) from type-2 but not from type-1 astrocytes. The effect does not seem to be related to cell swelling, which causes a different release profile in both type-1 and type-2 astrocytes. The absence of kainate- and quisqualate-evoked release in type-1 astrocytes suggests that the density of non-NMDA Receptors in this cell type is very low.

Pedro Boscan - One of the best experts on this subject based on the ideXlab platform.

  • Sensory afferent selective role of P2 Receptors in the nucleus tractus solitarii for mediating the cardiac component of the peripheral chemoReceptor reflex in rats.
    The Journal of physiology, 2002
    Co-Authors: Julian F. R. Paton, Patricia M. De Paula, K. Michael Spyer, Benedito H Machado, Pedro Boscan
    Abstract:

    We have assessed the functional role of type 2 purinergic (P2) Receptors within the caudal aspect of the commissural nucleus tractus solitarii (NTS) in mediating the peripheral chemoReceptor reflex cardiorespiratory response in the arterially perfused in situ working heart-brainstem preparation of rats. Microinjection in NTS of either suramin (100 pmol) or pyrinoxalphosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt (PPADS; 10 pmol) depressed the reflex bradycardia (by approximately 50 %), but not the tachypnoea, following peripheral chemoReceptor stimulation. In contrast, the reflex bradycardia produced by stimulation of pharyngo-oesophageal Receptors was unaffected. Furthermore, microinjections in NTS of the P2X Receptor agonist alpha,beta-methyleneadenosine 5'-triphosphate (10 pmol) evoked a bradycardia which was antagonized by suramin (100 pmol). This P2X agonist reversibly potentiated the peripheral chemoReceptor-evoked bradycardia. The effect of suramin was selective to purinergic Receptors because the bradycardia evoked by microinjection of alpha,beta-methyleneadenosine 5'-triphosphate was blocked while the bradycardic responses to microinjections of NMDA or non-NMDA Receptor Agonists were not affected. From whole-cell recordings, some NTS neurones received convergent excitatory synaptic inputs from both peripheral chemoReceptors and Receptors at the pharyngo-oesophageal junction. The excitatory postsynaptic response evoked by chemoReceptor stimulation was depressed by suramin, but convergent excitatory inputs from pharyngo-oesophageal Receptors were unperturbed. Our findings support the hypothesis that caudal commissural NTS P2 purinergic Receptors play a role in the neurotransmission of the parasympathetic (bradycardic) component of the chemoReceptor reflex. This effect is highly selective in that the chemoReceptor afferent-evoked tachypnoea, as well as other visceral Receptor-mediated reflex bradycardia, remain unaffected.

  • Sensory Afferent Selective Role of P2 Receptors in the Nucleus Tractus Solitarii for Mediating the Cardiac Component of the Peripheral ChemoReceptor Reflex in Rats
    The Journal of Physiology, 2002
    Co-Authors: Julian F. R. Paton, Patricia M. De Paula, K. Michael Spyer, Benedito H Machado, Pedro Boscan
    Abstract:

    We have assessed the functional role of type 2 purinergic (P2) Receptors within the caudal aspect of the commissural nucleus tractus solitarii (NTS) in mediating the peripheral chemoReceptor reflex cardiorespiratory response in the arterially perfused in situ working heart-brainstem preparation of rats. Microinjection in NTS of either suramin (100 pmol) or pyrinoxalphosphate-6-azophenyl-2′,4′-disulphonic acid tetrasodium salt (PPADS; 10 pmol) depressed the reflex bradycardia (by ≈50 %), but not the tachypnoea, following peripheral chemoReceptor stimulation. In contrast, the reflex bradycardia produced by stimulation of pharyngo-oesophageal Receptors was unaffected. Furthermore, microinjections in NTS of the P2X Receptor agonist α,β-methyleneadenosine 5′-triphosphate (10 pmol) evoked a bradycardia which was antagonized by suramin (100 pmol). This P2X agonist reversibly potentiated the peripheral chemoReceptor-evoked bradycardia. The effect of suramin was selective to purinergic Receptors because the bradycardia evoked by microinjection of α,β-methyleneadenosine 5′-triphosphate was blocked while the bradycardic responses to microinjections of NMDA or non-NMDA Receptor Agonists were not affected. From whole-cell recordings, some NTS neurones received convergent excitatory synaptic inputs from both peripheral chemoReceptors and Receptors at the pharyngo-oesophageal junction. The excitatory postsynaptic response evoked by chemoReceptor stimulation was depressed by suramin, but convergent excitatory inputs from pharyngo-oesophageal Receptors were unperturbed. Our findings support the hypothesis that caudal commissural NTS P2 purinergic Receptors play a role in the neurotransmission of the parasympathetic (bradycardic) component of the chemoReceptor reflex. This effect is highly selective in that the chemoReceptor afferent-evoked tachypnoea, as well as other visceral Receptor-mediated reflex bradycardia, remain unaffected.

Giulio Levi - One of the best experts on this subject based on the ideXlab platform.

  • astrocyte heterogeneity endogenous amino acid levels and release evoked by non n methyl d aspartate Receptor Agonists and by potassium induced swelling in type 1 and type 2 astrocytes
    Journal of Neurochemistry, 1992
    Co-Authors: Giulio Levi, Mario Patrizio
    Abstract:

    : The aim of the present study was to determine whether endogenous amino acids are released from type-1 and type-2 astrocytes following non-N-methyl-D-aspartate (NMDA) Receptor activation and whether such release is related to cell swelling. Amino acid levels and release were measured by HPLC in secondary cultures from neonatal rat cortex, highly enriched in type-1 or type-2 astrocytes. The following observations were made. (a) The endogenous level of several amino acids (glutamate, alanine, glutamine, asparagine, taurine, serine, and threonine) was substantially higher in type-1 than in type-2 astrocytes. (b) The spontaneous release of glutamine and taurine was higher in type-1 than in type-2 astrocytes; that of other amino acids was similar. (c) Exposure of type-2 astrocyte cultures to 50 microM kainate or quisqualate doubled the release of glutamate and caused a lower, but significant increase in that of aspartate, glycine, taurine, alanine, serine (only in the case of kainate), and glutamine (only in the case of quisqualate). These effects were reversed by the antagonist CNQX. (d) Exposure of type-1 astrocyte cultures to 50-200 microM kainate or 50 microM quisqualate did not affect endogenous amino acid release, even after treating the cultures with dibutyryl cyclic AMP. (e) Exposure of type-1 or type-2 astrocyte cultures to 50 mM KCl (replacing an equimolar concentration of NaCl) enhanced the release of taurine greater than glutamate greater than aspartate. The effect was somewhat more pronounced in type-2 than in type-1 astrocytes. Veratridine (50 microM) did not cause any increase in amino acid release. (f) The release of amino acids induced by high [K+] appeared to be related to cell swelling, in both type-1 and type-2 astrocytes. Swelling and K(+)-induced release were somewhat higher in type-2 than in type-1 astrocytes. In contrast, neither kainate nor quisqualate caused any appreciable increase in cell volume. It is concluded that non-NMDA Receptor Agonists stimulate the release of several endogenous amino acids (some of which are neuroactive) from type-2 but not from type-1 astrocytes. The effect does not seem to be related to cell swelling, which causes a different release profile in both type-1 and type-2 astrocytes. The absence of kainate- and quisqualate-evoked release in type-1 astrocytes suggests that the density of non-NMDA Receptors in this cell type is very low.

  • Astrocyte Heterogeneity: Endogenous Amino Acid Levels and Release Evoked by Non‐N‐Methyl‐D‐Aspartate Receptor Agonists and by Potassium‐Induced Swelling in Type‐1 and Type‐2 Astrocytes
    Journal of Neurochemistry, 1992
    Co-Authors: Giulio Levi, Mario Patrizio
    Abstract:

    : The aim of the present study was to determine whether endogenous amino acids are released from type-1 and type-2 astrocytes following non-N-methyl-D-aspartate (NMDA) Receptor activation and whether such release is related to cell swelling. Amino acid levels and release were measured by HPLC in secondary cultures from neonatal rat cortex, highly enriched in type-1 or type-2 astrocytes. The following observations were made. (a) The endogenous level of several amino acids (glutamate, alanine, glutamine, asparagine, taurine, serine, and threonine) was substantially higher in type-1 than in type-2 astrocytes. (b) The spontaneous release of glutamine and taurine was higher in type-1 than in type-2 astrocytes; that of other amino acids was similar. (c) Exposure of type-2 astrocyte cultures to 50 μM kainate or quisqualate doubled the release of glutamate and caused a lower, but significant increase in that of aspartate, glycine, taurine, alanine, serine (only in the case of kainate), and glutamine (only in the case of quisqualate). These effects were reversed by the antagonist CNQX. (d) Exposure of type-1 astrocyte cultures to 50–200 μM kainate or 50 μM quisqualate did not affect endogenous amino acid release, even after treating the cultures with dibutyryl cyclic AMP. (e) Exposure of type-1 or type-2 astrocyte cultures to 50 mM KCl (replacing an equimolar concentration of NaCl) enhanced the release of taurine > glutamate > aspartate. The effect was somewhat more pronounced in type-2 than in type-1 astrocytes. Veratridine (50 μM) did not cause any increase in amino acid release. (f) The release of amino acids induced by high [K+] appeared to be related to cell swelling, in both type-1 and type-2 astrocytes. Swelling and K+-induced release were somewhat higher in type-2 than in type-1 astrocytes. In contrast, neither kainate nor quisqualate caused any appreciable increase in cell volume. It is concluded that non-NMDA Receptor Agonists stimulate the release of several endogenous amino acids (some of which are neuroactive) from type-2 but not from type-1 astrocytes. The effect does not seem to be related to cell swelling, which causes a different release profile in both type-1 and type-2 astrocytes. The absence of kainate- and quisqualate-evoked release in type-1 astrocytes suggests that the density of non-NMDA Receptors in this cell type is very low.

Julian F. R. Paton - One of the best experts on this subject based on the ideXlab platform.

  • Sensory afferent selective role of P2 Receptors in the nucleus tractus solitarii for mediating the cardiac component of the peripheral chemoReceptor reflex in rats.
    The Journal of physiology, 2002
    Co-Authors: Julian F. R. Paton, Patricia M. De Paula, K. Michael Spyer, Benedito H Machado, Pedro Boscan
    Abstract:

    We have assessed the functional role of type 2 purinergic (P2) Receptors within the caudal aspect of the commissural nucleus tractus solitarii (NTS) in mediating the peripheral chemoReceptor reflex cardiorespiratory response in the arterially perfused in situ working heart-brainstem preparation of rats. Microinjection in NTS of either suramin (100 pmol) or pyrinoxalphosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt (PPADS; 10 pmol) depressed the reflex bradycardia (by approximately 50 %), but not the tachypnoea, following peripheral chemoReceptor stimulation. In contrast, the reflex bradycardia produced by stimulation of pharyngo-oesophageal Receptors was unaffected. Furthermore, microinjections in NTS of the P2X Receptor agonist alpha,beta-methyleneadenosine 5'-triphosphate (10 pmol) evoked a bradycardia which was antagonized by suramin (100 pmol). This P2X agonist reversibly potentiated the peripheral chemoReceptor-evoked bradycardia. The effect of suramin was selective to purinergic Receptors because the bradycardia evoked by microinjection of alpha,beta-methyleneadenosine 5'-triphosphate was blocked while the bradycardic responses to microinjections of NMDA or non-NMDA Receptor Agonists were not affected. From whole-cell recordings, some NTS neurones received convergent excitatory synaptic inputs from both peripheral chemoReceptors and Receptors at the pharyngo-oesophageal junction. The excitatory postsynaptic response evoked by chemoReceptor stimulation was depressed by suramin, but convergent excitatory inputs from pharyngo-oesophageal Receptors were unperturbed. Our findings support the hypothesis that caudal commissural NTS P2 purinergic Receptors play a role in the neurotransmission of the parasympathetic (bradycardic) component of the chemoReceptor reflex. This effect is highly selective in that the chemoReceptor afferent-evoked tachypnoea, as well as other visceral Receptor-mediated reflex bradycardia, remain unaffected.

  • Sensory Afferent Selective Role of P2 Receptors in the Nucleus Tractus Solitarii for Mediating the Cardiac Component of the Peripheral ChemoReceptor Reflex in Rats
    The Journal of Physiology, 2002
    Co-Authors: Julian F. R. Paton, Patricia M. De Paula, K. Michael Spyer, Benedito H Machado, Pedro Boscan
    Abstract:

    We have assessed the functional role of type 2 purinergic (P2) Receptors within the caudal aspect of the commissural nucleus tractus solitarii (NTS) in mediating the peripheral chemoReceptor reflex cardiorespiratory response in the arterially perfused in situ working heart-brainstem preparation of rats. Microinjection in NTS of either suramin (100 pmol) or pyrinoxalphosphate-6-azophenyl-2′,4′-disulphonic acid tetrasodium salt (PPADS; 10 pmol) depressed the reflex bradycardia (by ≈50 %), but not the tachypnoea, following peripheral chemoReceptor stimulation. In contrast, the reflex bradycardia produced by stimulation of pharyngo-oesophageal Receptors was unaffected. Furthermore, microinjections in NTS of the P2X Receptor agonist α,β-methyleneadenosine 5′-triphosphate (10 pmol) evoked a bradycardia which was antagonized by suramin (100 pmol). This P2X agonist reversibly potentiated the peripheral chemoReceptor-evoked bradycardia. The effect of suramin was selective to purinergic Receptors because the bradycardia evoked by microinjection of α,β-methyleneadenosine 5′-triphosphate was blocked while the bradycardic responses to microinjections of NMDA or non-NMDA Receptor Agonists were not affected. From whole-cell recordings, some NTS neurones received convergent excitatory synaptic inputs from both peripheral chemoReceptors and Receptors at the pharyngo-oesophageal junction. The excitatory postsynaptic response evoked by chemoReceptor stimulation was depressed by suramin, but convergent excitatory inputs from pharyngo-oesophageal Receptors were unperturbed. Our findings support the hypothesis that caudal commissural NTS P2 purinergic Receptors play a role in the neurotransmission of the parasympathetic (bradycardic) component of the chemoReceptor reflex. This effect is highly selective in that the chemoReceptor afferent-evoked tachypnoea, as well as other visceral Receptor-mediated reflex bradycardia, remain unaffected.

Rasmus P. Clausen - One of the best experts on this subject based on the ideXlab platform.

  • Stereoselective synthesis of novel 2'-(S)-CCG-IV analogues as potent NMDA Receptor Agonists.
    European journal of medicinal chemistry, 2020
    Co-Authors: Alex Maolanon, Athanasios Papangelis, David Kawiecki, Tung-chung Mou, Jed T. Syrenne, Kasper B. Hansen, Rasmus P. Clausen
    Abstract:

    We developed a versatile stereoselective route for the synthesis of new 2'-(S)-CCG-IV analogues. The route allows for late stage diversification and thereby provides access to a great variety of conformationally restricted cyclopropyl glutamate analogues. A selection of the 2'-(S)-CCG-IV analogues were evaluated using two-electrode voltage-clamp electrophysiology at recombinant GluN1/GluN2A-D Receptors, demonstrating that Agonists can be developed with GluN2 subunit-dependent potency and agonist efficacy. We also describe a crystal structure of the GluN2A agonist binding domain in complex with 2'-butyl-(S)-CCG-IV that determines the position of 2'-substituents in (S)-CCG-IV Agonists in the glutamate binding site and provides further insight to the structural determinants of their agonist efficacy. The stereoselective synthesis described here enables versatile and straight-forward modifications to diverse analogues of interest for the development of potent subtype-specific NMDA Receptor Agonists and other applications.

  • subtype specific Agonists for NMDA Receptor glycine binding sites
    ACS Chemical Neuroscience, 2017
    Co-Authors: Alex Maolanon, Athanasios Papangelis, Kasper B. Hansen, Rune Risgaard, Shuangyan Wang, Yoran Snoep, David C Holley, Anne F Barslund, Niels Svenstrup, Rasmus P. Clausen
    Abstract:

    A series of analogues based on serine as lead structure were designed, and their agonist activities were evaluated at recombinant NMDA Receptor subtypes (GluN1/2A-D) using two-electrode voltage-clamp (TEVC) electrophysiology. Pronounced variation in subunit-selectivity, potency, and agonist efficacy was observed in a manner that was dependent on the GluN2 subunit in the NMDA Receptor. In particular, compounds 15a and 16a are potent GluN2C-specific superAgonists at the GluN1 subunit with agonist efficacies of 398% and 308% compared to glycine. This study demonstrates that subunit-selectivity among glycine site NMDA Receptor Agonists can be achieved and suggests that glycine-site Agonists can be developed as pharmacological tool compounds to study GluN2C-specific effects in NMDA Receptor-mediated neurotransmission.