Glycine and kynurenate modulate the glutamate receptors in the myenteric plexus and in cortical membranes

Moroni, Flavio; Pellegrini‐Giampietro, Domenico E.; Alesiani, Marina; Cherici, Giovanna; Mori, Francesca; Galli, Alessandro

doi:10.1016/0014-2999(89)90404-4

Cited by 28 publications

(14 citation statements)

References 6 publications

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“…In particular, there is clear evidence for the presence of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype in the myenteric plexus [32]. It is this subtype which is preferentially activated by quinolinic acid and blocked by kynurenic acid [27], and its activation increases gut motility [22,25].…”

Section: Introductionmentioning

confidence: 99%

Purine, Kynurenine, Neopterin and Lipid Peroxidation Levels in Inflammatory Bowel Disease

et al. 2002

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The kynurenine metabolites of tryptophan may be involved in the regulation of neuronal activity and thus gut motility and secretion. We have now performed a pilot study to measure serum concentrations of purines and kynurenines in patients with mild inflammatory bowel disease, as well as in sex- and age-matched control subjects. For some analyses, the patients were subdivided into subgroups of those with Crohn’s disease and those with ulcerative colitis. The analyses indicated an increased activity in one branch of the kynurenine pathway. While there was no demonstrable difference in neopterin levels in either of the patient groups compared with controls, indicating that the disorders were in an inactive quiescent phase, both groups showed significantly higher levels of lipid peroxidation products. This suggests the presence of increased oxidative stress even during relative disease inactivity. The increased level of kynurenic acid may represent either a compensatory response to elevated activation of enteric neurones or a primary abnormality which induces a compensatory increase in gut activity. In either case, the data may indicate a role for kynurenine modulation of glutamate receptors in the symptoms of inflammatory bowel disease.

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Section: Introductionmentioning

confidence: 99%

Purine, Kynurenine, Neopterin and Lipid Peroxidation Levels in Inflammatory Bowel Disease

et al. 2002

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“…Ionotropic glutamate receptors which activate cation-selective receptor channels have been found in neurons and in glial cells [3] while outside the CNS, glutamate receptors have been described in several amphibian and insect preparations [4] as well as in mammalian peripheral tissue: specifically, we refer to guinea pig myenteric plexus [5, 6, 7], peripheral nerves [8] and a hamster kidney cell line [9]. The binding of [ 3 H]glutamate to adrenal gland membranes has been reported in a number of different species, including the rat [10, 11, 12].…”

Section: Introductionmentioning

confidence: 99%

Effect of Glutamate Receptor Agonists on Catecholamine Secretion in Bovine Chromaffin Cells

et al. 1998

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In this study, the effects of glutamate and glutamate receptor agonists in cultured chromaffin cells from bovine adrenal medulla were investigated. It was found that glutamate increases basal catecholamine (CA) secretion in a dose-dependent manner. This effect is mimicked by specific agonists of the four known glutamate receptors N-methyl-D-aspartate (NMDA), quisqualate/(RS)-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate (KA), and trans-(+)-1-amino-1,3-cyclopentane dicarboxylic acid (t-ACPD), which increased both basal and nicotine-evoked CA secretion. The NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid, 6-cyano-7-nitroquinoxaline-2,3-dione, an antagonist of KA and AMPA receptors, and L-(+)-2-amino-3-phosphonopropionic acid, an antagonist of the t-ACPD receptor, inhibited the stimulatory effect of related glutamate agonists. Hexamethonium, an antagonist of the nicotinic receptor, failed to influence glutamate agonists except for a 15% inhibition of KA. The increase in CA secretion produced by a 100 µM concentration of glutamate agonists was about 20–60% of that obtained with 10 µM of nicotine, an agonist of the physiological stimulatory cholinergic receptor. The increase in CA secretion produced by glutamate was accompanied by both an increase in bisoxonol fluorescence, suggesting membrane depolarization, and by an increase in intracellular Ca²⁺ concentrations. Results obtained with image analysis on single cells indicated that the percentage of cells which respond to the stimulation of 50 µM of glutamate is 42%. From these results, we conclude that glutamate, through its four known glutamate receptors, can increase both basal and nicotine-evoked CA secretion in chromaffin cells by a process which involves membrane depolarization and an increase in intracellular calcium levels.

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“…Their action was comparable to that of 7-Ci-KYNA I(1OiM) and KYNA (300yM) while DL-AP5 (100pM) behaved as a competitive antagonist (see also Moroni et al, 1989). The relative potencies of these compounds, calculated as their IC50s (i.e.…”

Section: Resultsmentioning

confidence: 90%

“…(0) (Birch et al, 1988b;Blake et al, 1988;Fletcher et al, 1988;Honore et al, 1988). Our experiments, performed in the guinea-pig ileum myenteric plexus, which is a pharmacological preparation suitable for the study of molecules interacting both with the glutamate and the glycine recognition sites of the NMDA receptor ion channel complex (Moroni et al, 1986;Luzzi et al, 1988;Moroni et al, 1989;Reggiani et al, 1989) (Erez et al, 1985;Frey et al, 1988). The micromolar concentrations of CNQX and DNQX used in some electrophysiological studies to block selectively non-NMDA receptors (Blake et al, 1988;McBain et al, 1988;Andreasen et al, 1989;Davies et al, 1989) were sufficient in the guinea-pig myenteric plexus to reduce the L-Glu-induced (NMDA receptor-mediated) ileal contraction.…”

Section: Resultsmentioning

confidence: 99%

“…As originally observed by Johnson & Ascher (1987) receptors. This occurs also in the guinea-pig myenteric plexus (Luzzi et al, 1988), while kynurenate (KNYA) competitively antagonizes glycine actions (Moroni et al, 1989). These observations make the guinea-pig ileum myenteric plexus a useful tool for studying agonists, antagonists and modulators of the NMDA receptor ion channel complex.…”

Section: Intoductionmentioning

confidence: 95%

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Quinoxalines interact with the glycine recognition site of NMDA receptors: studies in guinea‐pig myenteric plexus and in rat cortical membranes

Pellegrini‐Giampietro

Galli

Alesiani

et al. 1989

British J Pharmacology

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1 The effects of several quinoxalines, including 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7,dinitroquinoxaline-2,3-dione (DNQX), and of two kynurenates, kynurenate (KYNA) and 7-Clkynurenate (7-Cl-KYNA), have been evaluated on the N-methyl-D-aspartate (NMDA) receptors present in the guinea-pig ileum myenteric plexus preparation and on the strychnine-insensitive [3H]-glycine binding sites of cortical membranes. 2 Quinoxalines and kynurenates antagonized in a non-competitive manner L-glutamate-induced contraction. Their IC50s were (in uM): 5 for 7-Cl-KYNA, 7.5 for 6,7-Cl-3-hydroxy-2-quinoxaline carboxylate (6,7-Cl-HQCA), 20 for DNQX, 50 for CNQX, 76 for KYNA and 125 for 3-hydroxy-2-quinoxaline carboxylate (HQCA). 3 Glycine (5-50uM) completely reversed the antagonism displayed by both quinoxalines and kynurenates. The interaction between glycine and the tested compounds appeared to be competitive in nature. 6 These data show that quinoxalines and kynurenates may antagonize the responses to Lglutamate by interacting with the glycine recognition sites of the NMDA receptor ion channel complex. IntoductionThe quinoxalinediones, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, also known as FG9065) and 6,7, dinitroquinoxaline-2,3-dione (DNQX, FG9041), have been reported to be selective, potent and competitive antagonists for the quisqualate and the kainate subtypes of excitatory amino acid receptors (Honore' et al., 1988;Fletcher et al., 1988), and have therefore been proposed and utilized as powerful tools for detailed investigations on the physiological role of non N-methyl-D-aspartate (NMDA) receptors (Blake et al

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Glycine and kynurenate modulate the glutamate receptors in the myenteric plexus and in cortical membranes

Cited by 28 publications

References 6 publications

Purine, Kynurenine, Neopterin and Lipid Peroxidation Levels in Inflammatory Bowel Disease

Purine, Kynurenine, Neopterin and Lipid Peroxidation Levels in Inflammatory Bowel Disease

Effect of Glutamate Receptor Agonists on Catecholamine Secretion in Bovine Chromaffin Cells

Quinoxalines interact with the glycine recognition site of NMDA receptors: studies in guinea‐pig myenteric plexus and in rat cortical membranes

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