Synthesis of [3H]2-Amino-4-phosphonobutyric acid and characterization of its binding to rat brain membranes: a selective ligand for the chloride/calcium-dependent class ofl-glutamate binding sites

Monaghan, Daniel T.; McMills, Mark C.; Chamberlin, A. Richard; Cotman, Carl W.

doi:10.1016/0006-8993(83)90232-9

Cited by 74 publications

(47 citation statements)

References 25 publications

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“…The specific Na+-independent binding of L-[3HJ-glutamate was determined by a microcentrifugation procedure (Foster & Roberts, 1978 (adjusted to pH 6.8 at 32°C with acetic acid); these ionic conditions are optimal for the assay of Cl-/ Ca2l-dependent binding sites (Mena et al, 1982;Fagg et al, 1983a;Monaghan et al, 1983;Butcher et al, 1983;1984). After 30 min at 32°C, tubes were centrifuged for 3 min in an Eppendorf microcentrifuge and the supernatant was aspirated.…”

mentioning

confidence: 99%

Cl⁻/Ca²⁺‐dependent L‐glutamate binding sites do not correspond to 2‐amino‐4‐phosphonobutanoate‐sensitive excitatory amino acid receptors

Fagg¹,

Lanthorn²

1985

British J Pharmacology

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1 A series of phosphono and phosphino analogues of glutamate were used to compare the pharmacological properties of (a) ClP/Ca2+-dependent, 2-amino-4-phosphonobutanoate (AP4)-sen- (IC50 values> 1001iM). Inactive compounds which exhibited activity in the binding assay did not reverse the synaptic depressant effects of AP4, indicating that they were neither agonists nor antagonists at AP4-sensitive synapses. 4 The lack of correspondence between (a) the Cl-/Ca2 -dependent, AP4-sensitive population of L-[3H]-glutamate binding sites and (b) AP4-sensitive synaptic responses indicates that these binding sites are not the receptors through which AP4 exerts its neuropharmacological effects. The possibility that Cl-/Ca2+-dependent 'binding sites' represent transport into resealed SPM vesicles is discussed. 5 Electrophysiological data demonstrate that AP4-sensitive synaptic receptors display a high degree of ligand selectivity. High antagonist potency is shown only by glutamate analogues with unmodified a-amino and a-carboxyl groups, and with a bifunctional (dianionic) o-terminal.

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confidence: 99%

Cl⁻/Ca²⁺‐dependent L‐glutamate binding sites do not correspond to 2‐amino‐4‐phosphonobutanoate‐sensitive excitatory amino acid receptors

Fagg¹,

Lanthorn²

1985

British J Pharmacology

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“…It should be noted that the chloride-and calcium-sensitive Glu transport system is pharmacologically distinct from the classical Na + -and D-aspartate-sensitive Glu uptake site. There is currently no data on the action of L-PSer on this Glu uptake system but L-AP4 does not block Na ' -dependent Glu uptake (Balcar and Johnston, 1972;Vincent and McGeer, 1980;Monaghan et al, 1983). Data on the action of L-PSer at the Nat-dependent Glu uptake site would be helpful in gaining a better understanding of the pharmacology and physiology of this metabolite.…”

Section: Discussionmentioning

confidence: 99%

“…One of these sites is the [3H]AP4 binding site (Butcher et a!., 1983;Monaghan et al, 1983;Bridges et al, 1986), which appears to be the same as the chloride-and calcium-sensitive [ 3H]G1u binding site (Monaghan et at., (Kamiya et al, 1983) shown in two orthogonal views. Note the very similar orientation of all atoms, in particular, the charged amino, carboxyl, and phosphate (L-PSer) or phosphonate (L-AP4) group.…”

Section: Pharmacological Similarity Of L-pser and Lap4mentioning

confidence: 99%

“…Another separate site is the metabotropic receptor, which has a very different pharmacological profile most notably distinguished by potent action of L-AP3 at the metabotropic site without significant displacement of [ 3 HIAP4 (Butcher et al, 1983;Monaghan et al, 1983) or [ 3H]NAAG (Schoepp and Johnson, 1989). Another site, termed the AN receptor, is responsible for synaptic inhibition at a variety of sites in the brain (Bridges et al, 1986), but again, is pharmacologically distinguished from both the [ 3H]AP4 binding site and the metabotropic receptor by inactivity of QA at the AN receptor (Bridges et al, 1986;Forsythe and Clements, 1990), despite the high potency of QA in the other two systems (Butcher et al, 1983;Adamson et a!., 1990).…”

Section: Pharmacological Similarity Of L-pser and Lap4mentioning

confidence: 99%

“…Although this may decrease Ca"-dependent release, such an effect could increase Ca" -independentrelease (Nicholls, 1989). In this regard, it may be pertinent that QA, a potent displacer of [3H]AP4 binding (Butcher et al, 1983;Monaghan et al, 1983), induces a slow Ca" -independentrelease of Glu from synaptosomes (Nicholls, 1989). A second mechanism by which L-PSer could facilitate Glu release is suggested by studies on model membranes showing that all of the PME are capable of inducing the same changes in membrane phase that underlie the formation of vesicles and the fusion of vesicles with membrane bilayers.…”

Section: Molecular and Chemical Neuropathologymentioning

confidence: 99%

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Possible roles ofl-phosphoserine in the pathogenesis of Alzheimer’s disease

Klunk

McClure

Pettegrew

1991

Molecular and Chemical Neuropathology

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L-PhOSphoseflne is a membrane metabolite that is elevated in Alzheimer's disease brain. This compound has close structural similarity to L-glutamate. Electrophysiological studies indicate that L-phosphoserme has an acute inhibitory effect, but a delayed excitatory action. A hypothesis is developed based on pharmacological and electrophysiological studies that suggest that the inhibition may be mediated through presyrtaptic inhibition of L-glutamate release or perhaps antagonism of postsynaptic kainic acid receptors. The mechanism of the delayed excitation may lie in the tendency of L-phosphoserine to mimic the action of L-2-amino-4-phosphOnobutyric acid, a blocker of chloride-and calcium-sensitive L-glutamate transport. L-PhosphOserine has also been found to be a competitive antagonist at the N-methyl-o-aspartate recognition site and an antagonist of metabotropic receptor-mediated hydrolysis of inositol phospholipids. Because of these actions, there are several potentially important implications for the elevation of L-phosphoserme in Alzheimer's disease, including production memory impairment through presyn-

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N‐methyl‐D‐aspartate receptors, synaptic plasticity, and Alzheimer's disease

Cotman

Monaghan

Geddes

1989

Drug Development Research

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The NMDA (N-methyl-n-aspartate) excitatory amino acid receptor mediates a potent excitatory response in many regions of the CNS and plays a key role in excitotoxicity and synaptic plasticity. Results from radioligand-binding studies indicate that NMDA agonists and antagonists preferentially bind to differing populations of NMDA receptors. The distribution of NMDA receptors as labeled by the agonist L-[3H]glutamate differs from that obtained with the radiolabeled antagonist [3H]3-((?2-carboxypiperazine-4-yl)-propyl-lphosphonic acid ([3H]CPP). In addition, NMDA agonists and antagonists display complementary regional variations in their ability to displace L-[3H]glutamate binding. At least some of the differences between agonist and antagonist-binding properties can be accounted for by suggesting that glycine converts the NMDA receptor from an antagonist-preferring state into an agonist-preferring state. Since NMDA and other excitatory amino acid receptor functions are necessary for synaptic function, certain forms of synaptic plasticity, and learning, we have evaluated their status in Alzheimer's disease (AD). Using radioligandbinding techniques, we find that NMDA receptors are generally preserved in the course of AD pathology in the human hippocampus in spite of partial cell loss. Kainate receptors, on the other hand, display a redistribution within the hippocampus. This redistribution corresponds to an apparent synaptic reorganization owing to the loss of input from the entorhinal cortex. The response of both the NMDA and kainate receptor systems may be adaptive plastic responses that attempt to maintain hippocampal function that is compromised by AD. However, these mechanisms may also render the hippocampus more vulnerable to damage following excessive neuronal activation. Received final version

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Synthesis of [3H]2-Amino-4-phosphonobutyric acid and characterization of its binding to rat brain membranes: a selective ligand for the chloride/calcium-dependent class ofl-glutamate binding sites

Cited by 74 publications

References 25 publications

Cl⁻/Ca²⁺‐dependent L‐glutamate binding sites do not correspond to 2‐amino‐4‐phosphonobutanoate‐sensitive excitatory amino acid receptors

Cl⁻/Ca²⁺‐dependent L‐glutamate binding sites do not correspond to 2‐amino‐4‐phosphonobutanoate‐sensitive excitatory amino acid receptors

Possible roles ofl-phosphoserine in the pathogenesis of Alzheimer’s disease

N‐methyl‐D‐aspartate receptors, synaptic plasticity, and Alzheimer's disease

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Synthesis of [3H]2-Amino-4-phosphonobutyric acid and characterization of its binding to rat brain membranes: a selective ligand for the chloride/calcium-dependent class ofl-glutamate binding sites

Cited by 74 publications

References 25 publications

Cl−/Ca2+‐dependent L‐glutamate binding sites do not correspond to 2‐amino‐4‐phosphonobutanoate‐sensitive excitatory amino acid receptors

Cl−/Ca2+‐dependent L‐glutamate binding sites do not correspond to 2‐amino‐4‐phosphonobutanoate‐sensitive excitatory amino acid receptors

Possible roles ofl-phosphoserine in the pathogenesis of Alzheimer’s disease

N‐methyl‐D‐aspartate receptors, synaptic plasticity, and Alzheimer's disease

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Cl⁻/Ca²⁺‐dependent L‐glutamate binding sites do not correspond to 2‐amino‐4‐phosphonobutanoate‐sensitive excitatory amino acid receptors

Cl⁻/Ca²⁺‐dependent L‐glutamate binding sites do not correspond to 2‐amino‐4‐phosphonobutanoate‐sensitive excitatory amino acid receptors