Description

Metabotropic glutamate receptors (mGluR1-8) are G protein-coupled receptors that function to modulate brain excitatory signaling via presynaptic, postsynaptic, and glial mechanisms. DL-AP3 is a competitive mGluR1 antagonist that demonstrates a K_i value of 298 μM and an IC₅₀ value of 1mM for rat mGluR1α when challenged with glutamate. DL-AP3 can antagonize excitatory amino acid-induced phosphoinositide hydrolysis, induce Ca²⁺ mobilization in rat hippocampal slices, and inhibit phosphoserine phosphatase in rat brain cortex. At concentrations from 10-300 μM DL-AP3 has been used to characterize the role of mGluR in long-term potentiation in the hippocampus in a model of learning and memory, the release of glutamate in Parkinson’s disease, and the increased activity of mGluR implicated in fragile X syndrome.

Uses

DL-2-Amino-3-phosphonopropionic acid (AP3) is an inhibitor of phosphoserine phosphatase and mGluR. Also known as the antagonist of a receptor that is coupled to phosphoinositide metabolism in brain slices. D,L-2-Amino-3-phosphonopropionic acid is also an inhibitor of metabotropic glutamate receptors in rat brain.

Definition

ChEBI: 2-amino-3-phosphonopropanoic acid is a non-proteinogenc alpha-amino acid that is alanine in which one of the hydrogens of the terminal methyl group has been replaced by a dihydroxy(oxido)-lambda(5)-phosphanyl group. It has a role as a metabotropic glutamate receptor antagonist and a human metabolite. It is a non-proteinogenic alpha-amino acid, a member of phosphonic acids and an alanine derivative.

in vivo

IC 50

mGluR 1; mGluR 5

References

[1] DARRYLE D. SCHOEPP  James A M  David E Jane. Pharmacological agents acting at subtypes of metabotropic glutamate receptors[J]. Neuropharmacology, 1999, 38 10: Pages 1431-1476. DOI: 10.1016/s0028-3908(99)00092-1
[2] JON E. HAWKINSON  Paul L W  Manuel Acosta Burruel. The metabotropic glutamate receptor antagonist l-2-amino-3-phosphonopropionic acid inhibits phosphoserine phosphatase[J]. European journal of pharmacology, 1996, 307 2: Pages 219-225. DOI: 10.1016/0014-2999(96)00253-1
[3] S OTANI  W B L  J A Connor. Long-term potentiation and evidence for novel synaptic association in CA1 stratum oriens of rat hippocampus.[J]. Learning & memory, 1995, 2 2: 101-106. DOI: 10.1101/lm.2.2.101
[4] HAO LI  Gang H  Jian Hua Ding. Group I mGluR ligands fail to affect 6-hydroxydopamine- induced death and glutamate release of PC12 cells.[J]. Acta Pharmacologica Sinica, 2003, 24 7: 641-645.
[5] ZHAO-HUI XU. Group I mGluR antagonist rescues the deficit of D1-induced LTP in a mouse model of fragile X syndrome.[J]. Molecular Neurodegeneration, 2012, 7: 24. DOI: 10.1186/1750-1326-7-24