dizocilpine-maleate and 2-amino-3-phosphonopropionic-acid

The excitotoxicity cascade associated with energetic failure during and after cerebral ischemia involves the overactivation of glutamate receptors and intracellular calcium loading. We searched for synergistic neuroprotective effects of various drugs designed to prevent intracellular calcium influx in a model of oxygen-glucose deprivation (OGD) in cerebellar granule cells primary cultures. (5S,10R)-(-)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), D,L-2-Amino-3-phosphonopropionic acid (AP-3), 6-Cyano-7-nitroquinoxaline-2,3-dione disodium salt (CNQX) and Nifedipine were tested alone or in combinations. Treatments were applied during a two-hour OGD exposure and cellular outcome was assessed throughout 20-hour reoxygenation by the measurement of Propidium Iodide (PI) fluorescence. All treatments were able to prevent neuronal damage. OGD resulted in a mortality of 36.3±2.3% and 61.3±3.1% after 10 and 20 hours of reoxygenation, respectively. The most effective single treatment was AP-3 (3.3±1.4%; 17.9±2.6% mortality after 10 and 20 hours), followed in order by Nifedipine (7.2±1.6%; 20.1±3.0%), CNQX (8.5±2.5%; 20.0±3.5%), and MK-801 (14.9±2.6%; 39.3±6.4%). The combination of AP-3 with MK-801 showed a moderate synergistic effect (11.8±2.0% mortality at 20 hours), while the combinations of CNQX with Nifedipine and CNQX with MK-801, as well as the triple mix CNQX, Nifedipine and MK-801 failed to show a further improvement in the reduction of cellular death. In conclusion, targeting two mechanisms of cellular demise (ionotropic receptors and metabotropic glutamate receptors) provided an advantage against several unimodal strategies (blocking calcium entry through ionotropic glutamate receptors and L-type calcium channels). Our results suggest that a multimodal combinatorial treatment strategy in cerebral ischemia may increase neuroprotective efficacy and call for further research.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Alanine; Animals; Cell Death; Cells, Cultured; Cerebellum; Dizocilpine Maleate; Drug Therapy, Combination; Fluorescence; Glucose; Nifedipine; Oxygen; Propidium; Rats

Most in vitro models are only used to assess short-term effects of test compounds. However, as demonstrated here, hippocampal slice cultures can be used for long-term studies. The test compound used was the metabotropic glutamate receptor antagonist, L(+)-2-amino-3-phosphonopropionic acid (L-AP3), which is known to be toxic in vivo after subchronic, but not acute, administration. Degenerative effects were monitored by measuring the cellular uptake of propidium iodide (PI; continuously present in the medium) and lactate dehydrogenase (LDH) leakage, and by using a panel of histological stains. Hippocampal slices, derived from 2-3 day old rats and grown for 3 weeks, were subsequently exposed for the next 3 weeks to 0, 10 or 100microM L-AP3, with PI (2microM) in the culture medium. Exposure to 100microM L-AP3 induced severe toxicity after 4-6 days, shown by massive PI uptake, LDH leakage, changes in MAP2 and GFAP immunostaining, and in Nissl and Timm staining. In contrast, 10microM L-AP3 did not induce detectable neuronal degeneration. Treatment with the NMDA receptor antagonist, MK-801, or the AMPA/KA receptor antagonist NBQX, together with 100microM L-AP3, reduced neurodegeneration down to close to control values. It is concluded that continuous incubation of hippocampal slice cultures with PI is technically feasible for use in studies of inducible neuronal degeneration over time.

Topics: Alanine; Animal Testing Alternatives; Animals; Coloring Agents; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Hippocampus; L-Lactate Dehydrogenase; Propidium; Quinoxalines; Rats; Staining and Labeling; Tissue Culture Techniques

The present study investigated the involvement of spinal glutamate receptors in the induction and maintenance of the pain-related behaviors induced by the venom of scorpion Buthus martensi Karsch (BmK). (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-10-imine hydrogen maleate (MK-801; 40nmol; a non-competitive NMDA receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 40nmol; a non-NMDA receptor antagonist), dl-amino-3-phosphonopropionic acid (dl-AP3; 100nmol; a group I metabotropic glutamate receptor antagonist) and 4-aminopyrrolidine-2,4-dicarboxylate (APDC; 100nmol; a group II metabotropic glutamate receptor agonist) were employed. On intrathecal injection of glutamate receptor antagonists/agonist before BmK venom administration by 10min, BmK venom-induced spontaneous nociceptive responses could be suppressed by all tested agents. Primary thermal hyperalgesia could be inhibited by MK-801 and dl-AP3, while bilateral mechanical hyperalgesia could be inhibited by CNQX and dl-AP3 and contralateral mechanical hyperalgesia could be inhibited by APDC. On intrathecal injection of glutamate receptor antagonists/agonist after BmK venom injection by 4.5h, primary thermal hyperalgesia could be partially reversed by all tested agents, while bilateral mechanical hyperalgesia could only be inhibited by APDC. The results suggest that the role of spinal glutamate receptors may be different on the various manifestations of BmK venom-induced pain-related behaviors.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Alanine; Animals; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Injections, Spinal; Male; Pain; Proline; Rats; Rats, Sprague-Dawley; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Scorpion Venoms

The glucose deprivation-induced release of [3H]D-aspartate was studied in bovine and human retinas in a superfusion apparatus. [3H]D-aspartate release was significantly increased upon omitting glucose in the superfusion buffer. This effect was dependent on external Ca2+ because L- and N-type Ca2+-channel blockers, such as diltiazem (1 microM), nitrendipine (1 microM), and omega-conotoxin (100 nM), significantly reduced the effect of glucose-deprivation induced release of [3H]D-aspartate. Furthermore, while glutamate receptor agonists (L-glutamate, N-methyl-D-aspartate, but not kainate) potentiated the effects of glucose deprivation, antagonists (MK-801, MCPG, ifenprodil, and L-AP3) at these receptors blocked the glucose deprivation-induced release process. Taken together, these studies have demonstrated that under conditions of glucose deprivation, as may happen during ischemic events in vivo, the retinal glutamatergic nerve endings and/or glial cells promote the efflux of [3H]D-aspartate into the extracellular environment. This process appears to be receptor-mediated and dependent on extracellular Ca2+ and is similar to previous reports pertaining to brain tissues.

Topics: Alanine; Animals; Biguanides; Calcium Channel Blockers; Cattle; D-Aspartic Acid; Diltiazem; Dizocilpine Maleate; Drug Synergism; Glucose; Glutamic Acid; Glycine; Humans; Kainic Acid; N-Methylaspartate; Nitrendipine; omega-Conotoxins; Perfusion; Piperidines; Polyamines; Receptors, Glutamate; Retina; Tritium; Verapamil

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Alanine; Animals; Cell Survival; Cells, Cultured; Chick Embryo; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Methylmalonic Acid; Neurons; Neuroprotective Agents; Neurotoxins; NG-Nitroarginine Methyl Ester; Piperidines

In view of the neurotrophic effect of vasoactive intestinal peptide (VIP), the regulation of brain-derived neurotrophic factor (BDNF) expression by VIP and the related peptide pituitary adenylate cyclase-activating polypeptide (PACAP) was analysed by Northern blot in primary cultures of cortical neurones. Results reported in this article demonstrate that VIP and PACAP stimulate the expression of BDNF mRNA in primary cultures of cortical neurones and astrocytes. In primary cultures of cortical neurones, induction of BDNF mRNA by VIP and PACAP is completely inhibited by the N-methyl-D-aspartate (NMDA) receptor antagonists MK-801 and AP5, therefore indicating that VIP and PACAP do not stimulate BDNF expression directly but rather by potentiating the effect of glutamate tonically released by neurones and acting at NMDA receptors. In addition to its neurotrophic effects, BDNF has been shown to be involved in neuronal plasticity and results reported here suggest that by stimulating BDNF expression, VIP and PACAP could modulate synaptic plasticity in the cerebral cortex.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Alanine; Animals; Astrocytes; Blotting, Northern; Brain-Derived Neurotrophic Factor; Cells, Cultured; Cerebral Cortex; Dizocilpine Maleate; Drug Synergism; Excitatory Amino Acid Antagonists; Gene Expression; Glutamic Acid; Mice; Neuronal Plasticity; Neurons; Neuropeptides; Neurotransmitter Agents; Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, N-Methyl-D-Aspartate; RNA, Messenger; Vasoactive Intestinal Peptide

The activity of the neuroprotective agent clomethiazole at glutamate and ion channel sites has been investigated. Dizocilpine (3.25 mg/kg intraperitoneally) provided almost total protection against the damage produced by infusion of N-methyl-DL-aspartate (NMDLA; 75 micrograms) into the right hippocampus. In contrast, clomethiazole (96 mg/kg intraperitoneally) was without effect. Using ligand binding techniques, no evidence was found for clomethiazole interacting with NMDA, AMPA or sigma binding sites. Clomethiazole did inhibit the stimulatory effect of the metabotropic glutamate receptor agonist 1S3R-aminocyclopentone-1,3-dicarboxylic acid (ACPD) on phosphoinositol hydrolysis, but only at a concentration of 10(-3) M, which is unlikely to have functional relevance. Clomethiazole was also without effect on ligand binding to Ca2+ channels (N- or L- type), Na+ channels or ATP-sensitive K+ channels. Potentiation of GABA function therefore remains the most plausible explanation for the neuroprotective activity of clomethiazole.

Topics: Alanine; Animals; Chlormethiazole; Dizocilpine Maleate; Dose-Response Relationship, Drug; Hippocampus; Injections, Intraventricular; Ion Channels; Male; N-Methylaspartate; Neuroprotective Agents; Phosphatidylinositols; Rats; Receptors, Glutamate

1. Nitric oxide (NO) synthase activity was studied in slices of human temporal cortex samples obtained in neurosurgery by measuring the conversion of L-[3H]-arginine to L-[3H]-citrulline. 2. Elevation of extracellular K+ to 20, 35 or 60 mM concentration-dependently augmented L-[3H]-citrulline production. The response to 35 mM KCl was abolished by N(G)-nitro-L-arginine (100 microM) demonstrating NO synthase specific conversion of L-arginine to L-citrulline. Increasing extracellular MgCl2 concentration up to 10 mM also prevented the K+ (35 mM)-induced NO synthase activation, suggesting the absolute requirement of external calcium ions for enzyme activity. 3. However, the effect of high K+ (35 mM) on citrulline synthesis was insensitive to the antagonists of ionotropic and metabotropic glutamate receptors dizocilpine (MK-801), 6-nitro-7-sulphamoylbenzo(f)-quinoxaline-2-3-dione (NBQX) or L-2-amino-3-phosphonopropionic acid (L-AP3) as well as to the nicotinic receptor antagonist, mecamylamine. 4. The 35 mM K+ response was insensitive to omega-conotoxin GVIA (1 microM) and nifedipine (100 microM), but could be prevented in part by omega-agatoxin IVA (0.1 and 1 microM). The inhibition caused by 0.1 microM omega-agatoxin IVA (approximately 30%) was enhanced by adding omega-conotoxin GVIA (1 microM) or nifedipine (100 microM). Further inhibition (up to above 70%) could be observed when the three Ca2+ channel blockers were added together. Similarly, synthetic FTX 3.3 arginine polyamine (sFTX) prevented (50% at 100 microM) the K+-evoked NO synthase activation. This effect of sFTX was further enhanced (up to 70%) by adding 1 microM omega-conotoxin GVIA plus 100 microM nifedipine. No further inhibition could be observed upon addition of MK-801 or/and NBQX. 5. It was concluded that elevation of extracellular [K+] causes NO synthase activation by external Ca2+ entering cells mainly through channels of the P/Q-type. Other Ca2+ channels (L- and N-type) appear to contribute when P/Q-channels are blocked.

Topics: Alanine; Arginine; Calcium Channel Blockers; Calcium Channels; Citrulline; Dizocilpine Maleate; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Humans; In Vitro Techniques; Mecamylamine; Nicotinic Antagonists; Nitric Oxide Synthase; Nitroarginine; Potassium; Potassium Chloride; Quinoxalines; Temporal Lobe

Exposure of cultured cerebellar neurons to the putative metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionate (L-AP3) for 24 h produced a neurotoxic effect which was prevented by the addition of the NMDA receptor antagonist (+)-10,11-dihydro-5-methyl-5-H-dibenzo-[a,d]-cyclohepten-5,1 0-imine hydrogen maleate (MK-801). MK-801 did also reduce neurotoxicity following 72 h exposure to L-AP3 neurotoxicity in the presence of MK-801 was antagonized by glutamate. Our results suggest that metabotropic glutamate receptors may play an important role in neuronal survival by controlling NMDA receptor-dependent as well as independent pathways.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Alanine; Animals; Cell Survival; Cells, Cultured; Cerebellum; Dizocilpine Maleate; Neurons; Rats; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate

1. The contribution of various excitatory amino acid (EAA) receptors (NMDA, AMPA/kainate and metabotropic) in the brain to the development of morphine dependence was examined. This was performed by measuring the severity of the precipitated withdrawal syndrome following chronic subcutaneous (s.c.) morphine and intracerebroventricular (i.c.v.) EAA antagonist treatment. 2. Continuous subcutaneous (s.c.) treatment with morphine sulphate (36.65 mumol day-1) produced an intense and reliable naloxone-precipitated withdrawal syndrome. 3. Chronic i.c.v. treatment with antagonists selective for metabotropic and NMDA receptors, but not AMPA/kainate receptors, significantly attenuated abstinence symptoms. Conversely, EAA antagonists had very little effect on non-withdrawal behaviours. 4. These results suggest that, as well as changes elicited by activation of NMDA receptors, metabotropic receptors and intracellular changes in the phosphatidylinositol (PI) second-messenger system or the cyclic adenosine 3',5'-monophosphate (cAMP) second messenger system, to which EAA metabotropic receptors are linked, may be involved in the development of opioid dependence with chronic morphine treatment.

Topics: Alanine; Animals; Anti-Anxiety Agents; Behavior, Animal; Benzoates; Benzodiazepines; Dizocilpine Maleate; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Glycine; Injections, Intraventricular; Injections, Subcutaneous; Male; Morphine; Morphine Dependence; Rats; Receptors, AMPA; Receptors, Kainic Acid; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate; Substance Withdrawal Syndrome

We investigated the activation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) via stimulation of glutamate receptors and subsequent phosphorylation of vimentin and glial fibrillary acidic protein (GFAP) in cultured rat cortical astrocytes. The indirect immunofluorescence analysis with the anti-CaM kinase II antibody revealed that the enzyme was detected diffusely in the cytoplasm and more intensely in the nucleus. Glutamate elevated the Ca(2+)-independent activity of CaM kinase II through autophosphorylation, and this response was blocked by both DL-2-amino-3-phosphonopropionate and 6-cyano-7-nitroquinoxaline-2,3-dione, but not by D-2-amino-5-phosphonovalerate. In the experiments using 32P-labeled astrocytes, the phosphorylation of vimentin and GFAP as well as autophosphorylation of CaM kinase II were found to be stimulated after the exposure to glutamate. It was concluded by two-dimensional phosphopeptide analysis that the increased phosphorylation of vimentin and GFAP observed in intact cells were due to the activation of CaM kinase II by glutamate. These results suggest that glutamate can activate CaM kinase II through stimulation of both the metabotropic and non-N-methyl-D-aspartate receptors, and that the concomitant phosphorylation of vimentin and GFAP may in turn regulate the functions of intermediate filament proteins in intact astrocytes.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Alanine; Animals; Animals, Newborn; Astrocytes; Calcium-Calmodulin-Dependent Protein Kinases; Cells, Cultured; Cerebral Cortex; Dizocilpine Maleate; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Glutamates; Glutamic Acid; Immunoblotting; Ionomycin; Molecular Weight; Phosphoproteins; Phosphorylation; Quinoxalines; Rats; Rats, Wistar; Receptors, Glutamate; Tetradecanoylphorbol Acetate; Vimentin

The effects of dithiothreitol (DTT) and, reduced (GSH) and oxidized (GSSG), glutathione on the release of [3H]GABA evoked by glutamate and its agonists were studied in rat hippocampal slices. DTT had no effect on the basal release of [3H]GABA but it enhanced and prolonged the glutamate agonist-evoked release. This effect was abolished by (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohept-5,10-imine hydrogen maleate (MK-801), a noncompetitive NMDA antagonist, and blocked by Mg2+ ions. It was only slightly attenuated by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, and not affected by L-(+)-2-amino-3-phosphonopropionate (L-AP3), a selective antagonist of the metabotropic glutamate receptor. The effect of DTT on the NMDA-evoked release of GABA was only slightly affected by extracellular Ca2+ but completely blocked by verapamil even in the absence of Ca2+. GSH and GSSG attenuated or abolished the effects of DTT on the agonist-induced release of [3H]GABA. The results imply that the enhanced and prolonged release of GABA evoked by the coexistence of DTT and excitatory amino acids and attenuated by endogenous GSH and GSSG is a consequence of sustained activation of the NMDA receptor-governed ionophores, which contain functional thiol groups. DTT, GSH and GSSG may regulate the redox state and accessibility of these groups. In addition to the influx of extracellular Ca2+, DTT mobilizes Ca2+ from intracellular pools distinct from those regulated by metabotropic glutamate receptors.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Alanine; Animals; Dithiothreitol; Dizocilpine Maleate; GABA Agonists; gamma-Aminobutyric Acid; Glutathione; Glycine; Hippocampus; In Vitro Techniques; Kinetics; Magnesium; Male; N-Methylaspartate; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate; Tritium

We previously reported that trophic factors and neurotransmitters in concert regulate survival of cultured cerebellar Purkinje cells. In particular, excitatory amino acid (EAA) transmitters and NGF increased survival, whereas neither alone was effective. In the present studies, we sought to identify molecular mechanisms through which EAAs participate in the survival-promoting interaction. Initially, we characterized the potential role of ionotropic EAA receptors by exposing cultures to the antagonists MK-801, D-2-amino-5-phosphonovaleric acid, and 6,7-dinitroquinoxalinedione. Each increased cell number, suggesting that endogenous ionotropic activity decreased survival. To determine whether metabotropic EAA receptor stimulation modulates survival, the metabotropic agonist ACPD ([1S,3R]-1-aminocyclopentane-1,3-dicarboxylic acid; 1 microM) was tested. ACPD alone had no effect on survival. However, simultaneous exposure to ACPD and NGF significantly increased Purkinje number. Moreover, this increase in survival was blocked by L-AP3 [L(+)-2-amino-3-phosphonopropionic acid; 1 microM], a putative antagonist of certain metabotropic responses. L-AP3 also reduced cell number in the absence of exogenous EAA. Thus, endogenous metabotropic stimulation is normally necessary for survival. In sum, these studies reveal a novel mechanism whereby an excitatory neurotransmitter shapes neural development by simultaneous trophic and regressive actions that are, respectively, mediated by metabotropic and ionotropic EAA receptors.

Topics: 2-Amino-5-phosphonovalerate; Alanine; Animals; Cell Survival; Cells, Cultured; Cyclopentanes; Dizocilpine Maleate; Embryo, Mammalian; gamma-Aminobutyric Acid; Kinetics; Purkinje Cells; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, Amino Acid; Receptors, N-Methyl-D-Aspartate

The neuroprotective characteristics of the functional antagonist of metabotropic stimulated phosphoinositide hydrolysis, 2-amino-3-phosphonoproprionate (D,L-AP3), were examined alone and in combination with the non-competitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, against ibotenate induced brain injury. Postnatal day (PND) 7 rats received unilateral stereotaxic intrastriatal injections of 10 nmol ibotenate and treated with either D,L-AP3 (600 nmol i.c.), MK-801 (1 mg/kg i.p.) or both. The severity of brain injury was assessed on PND 12 by comparison of the weights of injected and contralateral cerebral hemispheres. Ibotenate induced injury was partially reduced by treatment with MK-801 (34.0 +/- 4.4% protection, P < 0.05 vs. PBS treated, independent t-test) but not D,L-AP3. However, combined treatment with both MK-801 and D,L-AP3 produced marked synergistic neuroprotection (83.5 +/- 7.6% protection, P < 0.001 vs. PBS treated, independent t-test). The data suggest that metabotropic stimulated phosphoinositide hydrolysis contributes to excitotoxic neuronal injury in the presence of concurrent ionotropic receptor activation.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Alanine; Animals; Brain; Brain Diseases; Dizocilpine Maleate; Drug Synergism; Female; Ibotenic Acid; Injections; Male; Organ Size; Quinoxalines; Rats; Rats, Sprague-Dawley

A detailed pharmacological characterization of the quisqualate (QA) receptor coupled to phospholipase C (Qp) was performed in striatal neurons. The experiments were carried out in the presence of the ionotropic antagonists MK-801 (1 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (30 microM), concentrations that block N-methyl-D-aspartate (NMDA) or alpha-amino-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in these cells. QA, ibotenate and trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD) evoked dose-dependent inositol phosphate formations with EC50 values of 0.3, 6.7 and 29 microM, respectively. QA and ibotenate had the same maximal effect (295.7 +/- 17.9% of basal, n = 6) whereas the efficacy of ACPD was somewhat lower (70.2 +/- 8.9% of the maximal quisqualate effect, n = 4). The QA-, ibotenate- and ACPD-induced maximal effects were not additive, and the inositol phosphate formations induced by high concentrations of L-aspartate (L-ASP), AMPA, kainate (KA) and domoate (DO) (100 microM or higher) were also not additive. The inositol phosphate responses induced by all these agonists were totally blocked by the phorbol ester phorbol 12,13-dibutyrate (PdBu), but not by atropine or prazosin suggesting that all these substances were able to stimulate the Qp excitatory amino acid receptor in striatal neurons. Of the excitatory amino acid receptor antagonists tested, only D,L-2-amino-3-phosphonopropionate (D,L-AP3) inhibited QA-induced InsP formation in a competitive manner (mean pKi = 4.45 +/- 0.43, n = 4). However, this drug was also a partial agonist of the Qp receptor since it stimulated the inositol phosphate formation. We found that D,L-AP3 also inhibited NMDA-induced calcium increase, in a competitive manner (mean pIC50 = 4.34 +/- 0.22, n = 8, and mean pKi = 3.7 +/- 0.11, n = 5). The Qp excitatory amino acid receptor in striatal neurons therefore closely resembles Qp receptors with high potency for agonists as described in striatal and retinal slices and synaptoneurosomes, and has several pharmacological differences compared to the Qp receptors which have low potency for agonists described in hippocampal and cortical slices, cerebellar granule cells, astrocytes and rat brain mRNA-injected oocytes.

Topics: 2-Aminoadipic Acid; 6-Cyano-7-nitroquinoxaline-2,3-dione; Alanine; Aminobutyrates; Animals; Cells, Cultured; Corpus Striatum; Dizocilpine Maleate; Fura-2; Ibotenic Acid; Inositol Phosphates; Kainic Acid; Mice; Neurons; Phorbol 12,13-Dibutyrate; Phosphoserine; Quinoxalines; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Type C Phospholipases