Enantioselective Synthesis of the Excitatory Amino Acid (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic Acid

2002 ◽  
Vol 67 (22) ◽  
pp. 7613-7617 ◽  
Author(s):  
Daniel M. Bradley ◽  
Renameditswe Mapitse ◽  
Nicholas M. Thomson ◽  
Christopher J. Hayes
Keyword(s):  
Amino Acid ◽  
Dicarboxylic Acid ◽  
Excitatory Amino Acid ◽  
Enantioselective Synthesis

Evidence for a kynurenate-insensitive glutamate receptor in nucleus tractus solitarii

1992 ◽  
Vol 262 (5) ◽  
pp. H1611-H1615 ◽  
Author(s):  
C. Pawloski-Dahm ◽  
F. J. Gordon
Keyword(s):  
Amino Acid ◽  
Dicarboxylic Acid ◽  
Receptor Antagonist ◽  
Glutamate Receptor ◽  
Excitatory Amino Acid ◽  
Cardiovascular Responses ◽  
Nucleus Tractus Solitarii ◽  
Baroreceptor Reflexes ◽  
Pharmacological Blockade ◽  
Baroreceptor Activation

Previous studies have shown that pharmacological blockade of ionotropic excitatory amino acid (EAA) receptors in the nucleus tractus solitarii (NTS) with kynurenate (Kyn) abolishes baroreceptor reflexes but fails to affect cardiovascular responses evoked by microinjections of L-glutamate (Glu) into the NTS. These observations have raised doubts as to whether Glu is a neurotransmitter of baroreceptor information in the NTS because the pharmacological actions of exogenously administered Glu are not identical to those of the neurotransmitter released in the NTS coincident with baroreceptor activation. One possible explanation for these results is that exogenously administered Glu might act at receptors that are not blocked by Kyn and are not accessible to synaptically released Glu in the NTS baroreflex pathway. The purpose of this study was to determine if Kyn-insensitive Glu receptors are present in the NTS. One candidate for this Kyn-insensitive receptor is the metabotropic EAA receptor that is selectively activated by trans-DL-1-amino-1,3-cyclopentane-dicarboxylic acid (ACPD). Microinjections of ACPD into the NTS of anesthetized rats produced dose-related depressor responses that were not reduced by Kyn or by pretreatment with the putative ACPD receptor antagonist L-2-amino-3-phosphonopropionate (L-AP-3). Similarly, depressor responses produced by Glu also were not affected by Kyn or by L-AP-3. These data demonstrate the presence of a Kyn-insensitive Glu receptor in the NTS. Moreover, they suggest that the failure of Kyn to reduce cardiovascular responses evoked by Glu injections into the NTS can be explained by an action of Glu at Kyn-insensitive ACPD receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals A voltage-clamp study of isolated stingray horizontal cell non-NMDA excitatory amino acid receptors

1989 ◽  
Vol 61 (1) ◽  
pp. 162-172 ◽  
Author(s):  
T. J. O'Dell ◽  
B. N. Christensen
Keyword(s):  
Amino Acid ◽  
Dicarboxylic Acid ◽  
Single Channel ◽  
Excitatory Amino Acid ◽  
Rank Order ◽  
Horizontal Cell ◽  
Channel Conductance ◽  
Single Channel Conductance ◽  
Open Time ◽  
The Mean

1. Horizontal cells enzymatically isolated from retinas of the Atlantic stingray (Dasyatis sabina) were voltage-clamped using the patch electrode in the whole-cell mode. A rapid microsuperfusion system was used to apply excitatory amino acid agonists and antagonists. 2. The isolated cells responded to glutamate (GLU), kainate (KA), quisqualate (QA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Responses elicited by GLU, QA, and AMPA but not KA exhibited a concentration-dependent and concanavalin A- (Con-A) sensitive desensitization. No responses were elicited by aspartate, N-methyl-D-aspartate, or quinolinate at concentrations as high as 1.0 mM. 3. Judging from the concentration producing one-half of the maximal current response (EC50), the rank order affinities of the agonists was QA greater than or equal to GLU greater than AMPA greater than KA. Whereas KA had the lowest affinity of the agonists tested it was the most efficacious, producing the largest currents. Hill coefficients of the concentration-response data were near two for KA and GLU and near one for QA and AMPA. 4. The agonists differed in their sensitivity to various excitatory amino acid receptor antagonists. Kynurenate (KYN) produced a nearly complete block of horizontal cell responses to GLU and KA at concentrations that had little effect on QA and AMPA. Piperidine-2,3-dicarboxylic acid (cis-PDA), 1-(4-chlorobenzoyl)-piperazine-2,3-dicarboxylic acid (pCB-PzDA), and folic acid were less potent antagonists than KYN but were also better blockers of KA and GLU responses than of QA- and AMPA-elicited responses. 5. When QA, AMPA, or GLU were applied in combination with 55.0 microM KA the current was less than that produced by KA alone. The rank order potency for the inhibition of KA-elicited responses was QA greater than AMPA greater than GLU. In the presence of low concentrations of KA (1.0-20.0 microM), QA- and AMPA-elicited responses were potentiated. This potentiation was prevented by KYN. 6. Single-channel conductance and mean open time were estimated from the current noise fluctuations in the presence of agonist. The mean single-channel conductance for QA was 9 pS that was almost twice as large as the conductance for KA (5.9 pS) and GLU (5.7 pS). The mean open time in the presence of QA or GLU was approximately 1 ms, which was about one-half of that for KA (2.0 ms). 7. These results are best explained by the existence of a single receptor protein with multiple but not identical ligand-binding sites.(ABSTRACT TRUNCATED AT 400 WORDS)

ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes

2002 ◽  
Vol 283 (2) ◽  
pp. C569-C578 ◽  
Author(s):  
Alexander A. Mongin ◽  
Harold K. Kimelberg
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Atp Release ◽  
Anion Channel ◽  
P2y Receptors ◽  
Cell Swelling ◽  
Channel Blockers ◽  
Medium Osmolarity ◽  
Subsequent Activation

Volume-dependent ATP release and subsequent activation of purinergic P2Y receptors have been implicated as an autocrine mechanism triggering activation of volume-regulated anion channels (VRACs) in hepatoma cells. In the brain ATP is released by both neurons and astrocytes and participates in intercellular communication. We explored whether ATP triggers or modulates the release of excitatory amino acid (EAAs) via VRACs in astrocytes in primary culture. Under basal conditions exogenous ATP (10 μM) activated a small EAA release in 70–80% of the cultures tested. In both moderately (5% reduction of medium osmolarity) and substantially (35% reduction of medium osmolarity) swollen astrocytes, exogenous ATP greatly potentiated EAA release. The effects of ATP were mimicked by P2Y agonists and eliminated by P2Y antagonists or the ATP scavenger apyrase. In contrast, the same pharmacological maneuvers did not inhibit volume-dependent EAA release in the absence of exogenous ATP, ruling out a requirement of autocrine ATP release for VRAC activation. The ATP effect in nonswollen and moderately swollen cells was eliminated by a 5–10% increase in medium osmolarity or by anion channel blockers but was insensitive to tetanus toxin pretreatment, further supporting VRAC involvement. Our data suggest that in astrocytes ATP does not trigger EAA release itself but acts synergistically with cell swelling. Moderate cell swelling and ATP may serve as two cooperative signals in bidirectional neuron-astrocyte communication in vivo.

scholarly journals Commissural Interneurons in Rhythm Generation and Intersegmental Coupling in the Lamprey Spinal Cord

1999 ◽  
Vol 81 (5) ◽  
pp. 2037-2045 ◽  
Author(s):  
James T. Buchanan
Keyword(s):  
Spinal Cord ◽  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Rhythmic Activity ◽  
Ventral Root ◽  
Rhythm Generation ◽  
Spinal Segment ◽  
Spinal Segments ◽  
Autocorrelation Method

Commissural interneurons in rhythm generation and intersegmental coupling in the lamprey spinal cord. To test the necessity of spinal commissural interneurons in the generation of the swim rhythm in lamprey, longitudinal midline cuts of the isolated spinal cord preparation were made. Fictive swimming was then induced by bath perfusion with an excitatory amino acid while recording ventral root activity. When the spinal cord preparation was cut completely along the midline into two lateral hemicords, the rhythmic activity of fictive swimming was lost, usually replaced with continuous ventral root spiking. The loss of the fictive swim rhythm was not due to nonspecific damage produced by the cut because rhythmic activity was present in split regions of spinal cord when the split region was still attached to intact cord. The quality of this persistent rhythmic activity, quantified with an autocorrelation method, declined with the distance of the split spinal segment from the remaining intact spinal cord. The deterioration of the rhythm was characterized by a lengthening of burst durations and a shortening of the interburst silent phases. This pattern of deterioration suggests a loss of rhythmic inhibitory inputs. The same pattern of rhythm deterioration was seen in preparations with the rostral end of the spinal cord cut compared with those with the caudal end cut. The results of this study indicate that commissural interneurons are necessary for the generation of the swimming rhythm in the lamprey spinal cord, and the characteristic loss of the silent interburst phases of the swimming rhythm is consistent with a loss of inhibitory commissural interneurons. The results also suggest that both descending and ascending commissural interneurons are important in the generation of the swimming rhythm. The swim rhythm that persists in the split cord while still attached to an intact portion of spinal cord is thus imposed by interneurons projecting from the intact region of cord into the split region. These projections are functionally short because rhythmic activity was lost within approximately five spinal segments from the intact region of spinal cord.

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