Effects of CNQX, APB, PDA, and kynurenate on horizontal cells of the tiger salamander retina

1989 ◽  
Vol 3 (3) ◽  
pp. 207-212 ◽  
Author(s):  
Xiong-Li Yang ◽  
Samuel M. Wu
Keyword(s):  
Dicarboxylic Acid ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Horizontal Cells ◽  
Tiger Salamander ◽  
Light Responses ◽  
Aspartate Receptor ◽  
Synaptic Receptors

AbstractEffects of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 2-amino-4-phosphonobutyrate (APB), cis-2,3-piperidine dicarboxylic acid (PDA), and kynurenate (KYN) on the depolarizing actions of glutamate and kainate on horizontal cells (HCs) were studied in the larval tiger salamander retina. APB, PDA, and KYN hyperpolarized the HCs, but they failed to block either the actions of glutamate and kainate, or the HC light responses. APB and PDA did not cause membrane polarizations in either rods or cones, suggesting that the HC hyperpolarizations were not mediated by presynaptic actions of these compounds. CNQX, the newly synthesized non-NMDA (N-Methyl-D-Aspartate) receptor antagonist, blocked the HC light responses and the action of kainate, but not that of glutamate. These results suggest that the synaptic receptors in the tiger salamander HCs are probably non-NMDA although extra-synaptic NMDA receptors may exist in these cells.

Coexistence and function of glutamate receptor subtypes in the horizontal cells of the tiger salamander retina

1991 ◽  
Vol 7 (4) ◽  
pp. 377-382 ◽  
Author(s):  
Xiong-Li Yang ◽  
Samuel M. Wu
Keyword(s):  
Dicarboxylic Acid ◽  
Propionic Acid ◽  
Glutamate Receptor ◽  
Horizontal Cells ◽  
Receptor Subtypes ◽  
Tiger Salamander ◽  
Light Responses ◽  
Receptor Agonists ◽  
Glutamate Receptor Agonists ◽  
And Function

AbstractEffects of the major glutamate receptor agonists, kainate (KA), α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), quisqualate (QA), N-methyl-D-aspartate (NMDA), L-α-amino-4-phosphonobutyrate (L-AP4), and trans-l-aminocyclopentane-1,3-dicarboxylic acid (ACPD) on horizontal cells (HCs) were studied in superfused larval tiger salamander retina. 20 μM of KA, AMPA, and QA mimicked the action of 3 mM glutamate in the absence and presence of 1 mM Co2+-20 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked the actions of KA and AMPA, but not those of QA and glutamate, indicative of the existence of CNQX-resistant QA receptors in the tiger salamander HCs. Prolonged application of ACPD hyperpolarized the HCs and enhanced the light responses, probably by shifting the resting HC voltage (Er) to a more hyperpolarized position. It is possible that the KA, AMPA, and CNQX-resistant QA receptors are involved in mediating the postsynaptic light responses in HCs, and ACPD receptors are involved in sensitivity adjustment of the HC responses.

The N-methyl-d-aspartate receptor antagonist MK-801 delays the onset of puberty and may acutely block the first spontaneous LH surge and ovulation in the rat

1991 ◽  
Vol 131 (3) ◽  
pp. 435-441 ◽  
Author(s):  
H. M. A. Meijs-Roelofs ◽  
P. Kramer ◽  
E. C. M. van Leeuwen
Keyword(s):  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Acute Treatment ◽  
Physiological Role ◽  
Female Rat ◽  
Mk 801 ◽  
Aspartate Receptor ◽  
Serum Lh ◽  
Lh Secretion

ABSTRACT The physiological role of activated hypothalamic N-methyl-d-aspartate (NMDA) receptors during the final phase of female sexual maturation was explored in the rat. The effects of administration of the specific non-competitive receptor antagonist MK-801 on the occurrence of first ovulation and on LH secretion were studied. Injections of MK-801 (0·1–0·2 mg/kg body wt, s.c.) were given once or twice daily, starting at 28 or 35 days of age and continuing up to the day of first ovulation, resulted in a significant delay of this ovulation. Rats that were treated daily with 0·2 mg MK-801/kg, starting on days 30 or 34 and continuing up to day 38, but not including the day of first pro-oestrus, also showed retarded first ovulation. No decrease in serum LH concentration, compared with control rats, could be detected in these rats. Acute treatment with MK-801 (one or two injections of 0·2, or one injection of 0·5 mg/kg) given at 11.30 h (and 16.00 h) on the day of first pro-oestrus produced partial (1 × 0·2 mg/kg) or complete (2×0·2 and 1 × 0·5 mg/kg) blockade of first ovulation; blocked rats ovulated 1 day later. Serum LH concentrations at 16.00 h on the day of pro-oestrus were significantly decreased in all MK-801-treated groups compared with saline-injected control rats. At 19.00 and 22.00 h LH concentrations remained low in all non-ovulating MK-801-treated rats, but increased in the MK-801-treated rats that ovulated. Thus chronic blockade of the NMDA receptors by the antagonist MK-801 delays but does not prevent first ovulation, whereas acute treatment blocks the pro-oestrous LH peak. It was concluded that activation of NMDA receptors plays an important role both in tonic and preovulatory LH secretion during the onset of puberty in the female rat. Journal of Endocrinology (1991) 131, 435–441

Identification of glutamate receptor subtypes mediating inputs to bipolar cells and ganglion cells in the tiger salamander retina

1993 ◽  
Vol 69 (6) ◽  
pp. 2099-2107 ◽  
Author(s):  
S. H. Hensley ◽  
X. L. Yang ◽  
S. M. Wu
Keyword(s):  
Receptor Antagonist ◽  
Glutamate Receptor ◽  
Ganglion Cells ◽  
Extracellular Recording ◽  
Bipolar Cells ◽  
Receptor Subtypes ◽  
Tiger Salamander ◽  
Light Onset ◽  
Light Responses ◽  
Onset Responses

1. The effects of glutamate receptor agonists and antagonists on bipolar cells and ganglion cells were studied with the use of intracellular and extracellular recording in the superfused, isolated, flat-mounted tiger salamander retina. The goal of the experiments was to correlate glutamate receptor subtypes with their localization at specific synaptic sites in the tiger salamander retina. The drugs tested were the kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the N-methyl-D-aspartate (NMDA) receptor antagonist 3-(C+/-)-2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP) and L-2-amino-4-phosphonobutyrate (L-AP4). 2. The light responses of hyperpolarizing bipolar cells were suppressed by 20 microM CNQX, whereas L-AP4 had no effect on their light responses. In contrast, 20 microM CNQX had no effect on depolarizing bipolar cells, whereas L-AP4 abolished the light responses of these cells. 3. The light offset responses of OFF and ON-OFF ganglion cells were completely blocked by concentrations of CNQX as low as 5 microM. The light onset responses of ON-OFF ganglion cells were blocked when the concentration of CNQX was raised to 20 microM. In addition, 30 microM CPP partially blocked the light onset responses of ON-OFF ganglion cells but had a lesser effect on the light offset responses. 4. Twenty micromolars of CNQX blocked a transient component, and 20 microM CPP blocked a sustained component of the light response of sustained-ON ganglion cells.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals I4AA-Sensitive Chloride Current Contributes to the Center Light Responses of Bipolar Cells in the Tiger Salamander Retina

2000 ◽  
Vol 83 (6) ◽  
pp. 3473-3482 ◽  
Author(s):  
Fan Gao ◽  
Bruce R. Maple ◽  
Samuel M. Wu
Keyword(s):  
Receptor Antagonist ◽  
Bipolar Cell ◽  
Reversal Potential ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Chloride Current ◽  
Tiger Salamander ◽  
Light Responses ◽  
Chloride Currents ◽  
Axon Terminals

Light-evoked currents in depolarizing and hyperpolarizing bipolar cells (DBCs and HBCs) were recorded under voltage-clamp conditions in living retinal slices of the larval tiger salamander. Responses to illumination at the center of the DBCs' and HBCs' receptive fields were mediated by two postsynaptic currents: Δ I C, a glutamate-gated cation current with a reversal potential near 0 mV, and Δ I Cl, a chloride current with a reversal potential near −60 mV. In DBCs Δ I C was suppressed byl-2-amino-4-phosphonobutyric acid (l-AP4), and in HBCs it was suppressed by 6,7-dinitroquinoxaline-2,3-dione (DNQX). In both DBCs and HBCs Δ I Cl was suppressed by imidazole-4-acetic acid (I4AA), a GABA receptor agonist and GABAC receptor antagonist. In all DBCs and HBCs examined, 10 μM I4AA eliminated Δ I Cl and the light-evoked current became predominately mediated by Δ I C. The addition of 20 μM l-AP4 to the DBCs or 50 μM DNQX to HBCs completely abolished Δ I C. Focal application of glutamate at the inner plexiform layer elicited chloride currents in bipolar cells by depolarizing amacrine cells that release GABA at synapses on bipolar cell axon terminals, and such glutamate-induced chloride currents in DBCs and HBCs could be reversibly blocked by 10 μM I4AA. These experiments suggest that the light-evoked, I4AA-sensitive chloride currents (Δ I Cl) in DBCs and HBCs are mediated by narrow field GABAergic amacrine cells that activate GABACreceptors on bipolar cell axon terminals. Picrotoxin (200 μM) or (1,2,5,6-tetrahydropyridine-4yl) methyphosphinic acid (TPMPA) (2 other GABAC receptor antagonists) did not block (but enhanced and broadened) the light-evoked Δ I Cl, although they decreased the chloride current induced by puff application of GABA or glutamate. The light response of narrow field amacrine cells were not affected by I4AA, but were substantially enhanced and broadened by picrotoxin. These results suggest that there are at least two types of GABACreceptors in bipolar cells: one exhibits stronger I4AA sensitivity than the other, but both can be partially blocked by picrotoxin. The GABA receptors in narrow field amacrine cells are I4AA insensitive and picrotoxin sensitive. The light-evoked Δ I Cl in bipolar cells are mediated by the more strongly I4AA-sensitive GABAC receptors. Picrotoxin, although acting as a partial GABAC receptor antagonist in bipolar cells, does not suppress Δ I Clbecause its presynaptic effects on amacrine cell light responses override its antagonistic postsynaptic actions.

Activation of NMDA receptors produces dopamine-mediated changes in fish retinal horizontal cell light responses

1996 ◽  
Vol 75 (2) ◽  
pp. 629-647 ◽  
Author(s):  
K. Harsanyi ◽  
Y. Wang ◽  
S. C. Mangel
Keyword(s):  
Nmda Receptors ◽  
Horizontal Cell ◽  
Horizontal Cells ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Light Stimulation ◽  
Light Responses ◽  
Full Field ◽  
Flickering Light

1. The action of N-methyl-D-aspartate (NMDA) on cone horizontal cells was studied in in vitro goldfish retinas superfused with a bicarbonate-based Ringer solution that contained D-serine (0.5 microM), a glycine analogue, but no added Mg2+. Horizontal cell light responses and electrical coupling were assessed by monitoring responses to full-field stimuli and to small, centered (0.4 mm diam) spots of light, respectively. 2. NMDA uncoupled horizontal cells, reduced their light responsiveness, and acted in a dose-dependent manner, with threshold at 10 microM and maximum effect at 100 microM. 3. Application of the NMDA antagonists DL-2-amino-7-phosphonoheptanoic acid-AP-5) or D-2-amino-5-phosphonopentanoic acid-AP-5) (50 microM) blocked the uncoupling action of NMDA (100 microM), as did prior application of SCH23390, a dopamine D1 antagonist, or prior treatment of the retinas with 6-hydroxydopamine, a procedure that destroys dopaminergic neurons. 4. Addition of Mg2+ (1 mM) partially blocked the effects of NMDA at 100 microM and completely blocked the effects of 50 microM NMDA. The effects of NMDA (50 or 100 microM) were also reduced if it was applied without D-serine. 5. Both flickering (5 Hz) and sustained light stimulation uncoupled horizontal cells and reduced their light responsiveness. Application of AP-7 blocked the effects of flickering light stimulation, but did not block the effects of sustained light. 6. These results suggest that activation of NMDA receptors in the fish retina uncouples cone horizontal cells and decreases their light responsiveness by increasing dopamine release. The results further suggest that flickering light, but not sustained light, increases the release of dopamine through activation of NMDA receptors.

scholarly journals Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat

2021 ◽  
Author(s):  
Hong Wei ◽  
Zuyue Chen ◽  
Ari Koivisto ◽  
Antti Pertovaara
Keyword(s):  
Amino Acid ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Gap Junction ◽  
Male Rats ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Mk 801 ◽  
Mechanical Hypersensitivity ◽  
Pain Hypersensitivity

Abstract Background Earlier studies show that endogenous sphingolipids can induce pain hypersensitivity, activation of spinal astrocytes, release of proinflammatory cytokines and activation of TRPM3 channel. Here we studied whether the development of pain hypersensitivity induced by sphingolipids in the spinal cord can be prevented by pharmacological inhibition of potential downstream mechanisms that we hypothesized to include TRPM3, σ1 and NMDA receptors, gap junctions and D-amino acid oxidase. Methods Experiments were performed in adult male rats with a chronic intrathecal catheter for spinal drug administrations. Mechanical nociception was assessed with monofilaments and heat nociception with radiant heat. N,N-dimethylsphingosine (DMS) was administered to induce pain hypersensitivity. Ononetin, isosakuranetin, naringenin (TRPM3 antagonists), BD-1047 (σ1 receptor antagonist), carbenoxolone (a gap junction decoupler), MK-801 (NMDA receptor antagonist) and AS-057278 (inhibitor of D-amino acid oxidase, DAAO) were used to prevent the DMS-induced hypersensitivity, and pregnenolone sulphate (TRPM3 agonist) to recapitulate hypersensitivity. Results DMS alone produced within 15 min a dose-related mechanical hypersensitivity that lasted at least 24 h, without effect on heat nociception. Preemptive treatments with ononetin, isosakuranetin, naringenin, BD-1047, carbenoxolone, MK-801 or AS-057278 attenuated the development of the DMS-induced hypersensitivity, but had no effects when administered alone. Pregnenolone sulphate (TRPM3 agonist) alone induced a dose-related mechanical hypersensitivity that was prevented by ononetin, isosakuranetin and naringenin. Conclusions Among spinal pronociceptive mechanisms activated by DMS are TRPM3, gap junction coupling, the σ1 and NMDA receptors, and DAAO.

scholarly journals Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

2011 ◽  
Vol 301 (2) ◽  
pp. R448-R455 ◽  
Author(s):  
Jason Wright ◽  
Carlos Campos ◽  
Thiebaut Herzog ◽  
Mihai Covasa ◽  
Krzysztof Czaja ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Nmda Receptor Antagonist ◽  
Behavioral Pattern ◽  
Vagal Afferents ◽  
Nmda Receptor Antagonists ◽  
The Brain

Intraperitoneal injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of d-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (d-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, d-CPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.

Amacrine and ganglion cell contributions to the electroretinogram in amphibian retina

2001 ◽  
Vol 18 (1) ◽  
pp. 147-156 ◽  
Author(s):  
GAUTAM AWATRAMANI ◽  
JUE WANG ◽  
MALCOLM M. SLAUGHTER
Keyword(s):  
Contrast Agents ◽  
Ganglion Cell ◽  
Neuronal Activity ◽  
Opposite Effect ◽  
Cell Function ◽  
Ganglion Cells ◽  
Field Potential ◽  
Tiger Salamander ◽  
Third Order ◽  
Light Responses

The neuronal generators of the b- and d-waves of the electroretinogram (ERG) were investigated in the tiger salamander retina to determine if amacrine and ganglion cells contribute to this field potential. Several agents were used that affect third-order neurons, such as tetrodotoxin, baclofen, and NMDA agonists and antagonists. Baclofen, an agent that enhances light responses in third-order neurons, increased the d-wave and reduced the b-wave. In contrast, agents that decrease light responses in third-order neurons had the opposite effect of enhancing the b-wave and depressing the d-wave. The effect on the d-wave was particularly pronounced. The results indicate that third-order neuronal activity influences b- and d-waves of the ERG. The opposing actions suggest that the b-wave to d-wave ratio might serve as an measure of ganglion cell function.

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